TY  - JOUR
AU  - Račić, Anđelka
AU  - Jurišić-Dukovski, Bisera
AU  - Lovrić, Jasmina
AU  - Dobričić, Vladimir
AU  - Vučen, Sonja
AU  - Micov, Ana
AU  - Stepanović-Petrović, Radica
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Bajac, Jelena
AU  - Krajišnik, Danina
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5610
AB  - The incorporation of polymers into drug delivery vehicles has been shown to be a useful approach to prolong the
residence time of drugs in the precorneal tear film and to improve penetration into biological membranes. The
main objective of this research was to formulate novel viscous eye drops with ketotifen as the active ingredient,
containing the polysaccharides: chitosan (MCH), hydroxypropyl guar gum (HPG) and hyaluronic acid (SH) alone
and in combination as functional polymers. DSC and FT-IR techniques showed the compatibility between
ketotifen and polymers. Physicochemical and rheological analysis at ambient and simulated physiological conditions, as well as the evaluation of mucoadhesive properties showed that vehicles containing combinations of
polymers have suitable physicochemical and functional properties with demonstrated synergism between
combined polymers (MCH and HPG i.e. SH and HPG). The drug permeability was successfully estimated in vitro
using HCE-T cell-based models. MTT cytotoxicity assay demonstrates that the tested formulations were non-toxic
and well tolerated. In vivo preclinical study on mice revealed that both vehicles containing mixed polymers
enhanced and prolonged the antipruritic/analgesic-like effect of ophthalmic ketotifen. Based on these results,
both combinations of polysaccharide polymers, especially SH-HPG, could be considered as potential new carriers
for ketotifen for ophthalmic use.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Synergism of polysaccharide polymers in antihistamine eye drops: Influence on physicochemical properties and in vivo efficacy
VL  - 655
SP  - 124033
DO  - 10.1016/j.ijpharm.2024.124033
ER  - 

@article{
author = "Račić, Anđelka and Jurišić-Dukovski, Bisera and Lovrić, Jasmina and Dobričić, Vladimir and Vučen, Sonja and Micov, Ana and Stepanović-Petrović, Radica and Tomić, Maja and Pecikoza, Uroš and Bajac, Jelena and Krajišnik, Danina",
year = "2024",
abstract = "The incorporation of polymers into drug delivery vehicles has been shown to be a useful approach to prolong the
residence time of drugs in the precorneal tear film and to improve penetration into biological membranes. The
main objective of this research was to formulate novel viscous eye drops with ketotifen as the active ingredient,
containing the polysaccharides: chitosan (MCH), hydroxypropyl guar gum (HPG) and hyaluronic acid (SH) alone
and in combination as functional polymers. DSC and FT-IR techniques showed the compatibility between
ketotifen and polymers. Physicochemical and rheological analysis at ambient and simulated physiological conditions, as well as the evaluation of mucoadhesive properties showed that vehicles containing combinations of
polymers have suitable physicochemical and functional properties with demonstrated synergism between
combined polymers (MCH and HPG i.e. SH and HPG). The drug permeability was successfully estimated in vitro
using HCE-T cell-based models. MTT cytotoxicity assay demonstrates that the tested formulations were non-toxic
and well tolerated. In vivo preclinical study on mice revealed that both vehicles containing mixed polymers
enhanced and prolonged the antipruritic/analgesic-like effect of ophthalmic ketotifen. Based on these results,
both combinations of polysaccharide polymers, especially SH-HPG, could be considered as potential new carriers
for ketotifen for ophthalmic use.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Synergism of polysaccharide polymers in antihistamine eye drops: Influence on physicochemical properties and in vivo efficacy",
volume = "655",
pages = "124033",
doi = "10.1016/j.ijpharm.2024.124033"
}

Račić, A., Jurišić-Dukovski, B., Lovrić, J., Dobričić, V., Vučen, S., Micov, A., Stepanović-Petrović, R., Tomić, M., Pecikoza, U., Bajac, J.,& Krajišnik, D.. (2024). Synergism of polysaccharide polymers in antihistamine eye drops: Influence on physicochemical properties and in vivo efficacy. in International Journal of Pharmaceutics
Elsevier., 655, 124033.
https://doi.org/10.1016/j.ijpharm.2024.124033

Račić A, Jurišić-Dukovski B, Lovrić J, Dobričić V, Vučen S, Micov A, Stepanović-Petrović R, Tomić M, Pecikoza U, Bajac J, Krajišnik D. Synergism of polysaccharide polymers in antihistamine eye drops: Influence on physicochemical properties and in vivo efficacy. in International Journal of Pharmaceutics. 2024;655:124033.
doi:10.1016/j.ijpharm.2024.124033 .

Račić, Anđelka, Jurišić-Dukovski, Bisera, Lovrić, Jasmina, Dobričić, Vladimir, Vučen, Sonja, Micov, Ana, Stepanović-Petrović, Radica, Tomić, Maja, Pecikoza, Uroš, Bajac, Jelena, Krajišnik, Danina, "Synergism of polysaccharide polymers in antihistamine eye drops: Influence on physicochemical properties and in vivo efficacy" in International Journal of Pharmaceutics, 655 (2024):124033,
https://doi.org/10.1016/j.ijpharm.2024.124033 . .

TY  - JOUR
AU  - Nastić, Katarina
AU  - Pecikoza, Uroš
AU  - Labudović-Borović, Milica
AU  - Kotur-Stevuljević, Jelena
AU  - Micov, Ana
AU  - Jovanović, Aleksandar
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5018
AB  - Osteoarthritis represents a leading cause of disability with limited treatment options. Furthermore, it is frequently accompanied by cardiovascular and cognitive disorders, which can be exacerbated by osteoarthritis or drugs used for its treatment. Here, we examined the behavioral and cardiac effects of the novel antidepressant vortioxetine in an osteoarthritis model, and compared them to duloxetine (an established osteoarthritis treatment). Osteoarthritis was induced in male and female rats with an intraarticular sodium-monoiodoacetate injection. Antidepressants were orally administered for 28 days following induction. During this period the acetone, burrowing and novel-object-recognition tests (NORT) were used to assess the effects of antidepressants on pain hypersensitivity (cold allodynia), animal well-being and cognitive performance, respectively. Following behavioral experiments, heart muscles were collected for assessment of redox status/histology. Antidepressant treatment dose-dependently reduced cold allodynia in rats with osteoarthritis. Duloxetine (but not vortioxetine) depressed burrowing behavior in osteoarthritic rats in a dose-related manner. Osteoarthritis induction reduced cognitive performance in NORT, which was dose-dependently alleviated by vortioxetine (duloxetine improved performance only in female rats). Furthermore, duloxetine (but not vortioxetine) increased oxidative stress parameters in the heart muscles of female (but not male) rats and induced histological changes in cardiomyocytes indicative of oxidative damage. Vortioxetine displayed comparable efficacy to duloxetine in reducing pain hypersensitivity. Furthermore, vortioxetine (unlike duloxetine) dose-dependently improved cognitive performance and had no adverse effect on burrowing behavior (animal surrogate of well-being) and cardiac redox status/histology. Our results indicate that vortioxetine could be a potential osteoarthritis treatment (with better characteristics compared to duloxetine).
PB  - Elsevier Masson
T2  - Biomedicine and Pharmacotherapy
T1  - The antidepressant drugs vortioxetine and duloxetine differentially and sex-dependently affect animal well-being, cognitive performance, cardiac redox status and histology in a model of osteoarthritis
VL  - 166
DO  - 10.1016/j.biopha.2023.115360
ER  - 

@article{
author = "Nastić, Katarina and Pecikoza, Uroš and Labudović-Borović, Milica and Kotur-Stevuljević, Jelena and Micov, Ana and Jovanović, Aleksandar and Tomić, Maja and Stepanović-Petrović, Radica",
year = "2023",
abstract = "Osteoarthritis represents a leading cause of disability with limited treatment options. Furthermore, it is frequently accompanied by cardiovascular and cognitive disorders, which can be exacerbated by osteoarthritis or drugs used for its treatment. Here, we examined the behavioral and cardiac effects of the novel antidepressant vortioxetine in an osteoarthritis model, and compared them to duloxetine (an established osteoarthritis treatment). Osteoarthritis was induced in male and female rats with an intraarticular sodium-monoiodoacetate injection. Antidepressants were orally administered for 28 days following induction. During this period the acetone, burrowing and novel-object-recognition tests (NORT) were used to assess the effects of antidepressants on pain hypersensitivity (cold allodynia), animal well-being and cognitive performance, respectively. Following behavioral experiments, heart muscles were collected for assessment of redox status/histology. Antidepressant treatment dose-dependently reduced cold allodynia in rats with osteoarthritis. Duloxetine (but not vortioxetine) depressed burrowing behavior in osteoarthritic rats in a dose-related manner. Osteoarthritis induction reduced cognitive performance in NORT, which was dose-dependently alleviated by vortioxetine (duloxetine improved performance only in female rats). Furthermore, duloxetine (but not vortioxetine) increased oxidative stress parameters in the heart muscles of female (but not male) rats and induced histological changes in cardiomyocytes indicative of oxidative damage. Vortioxetine displayed comparable efficacy to duloxetine in reducing pain hypersensitivity. Furthermore, vortioxetine (unlike duloxetine) dose-dependently improved cognitive performance and had no adverse effect on burrowing behavior (animal surrogate of well-being) and cardiac redox status/histology. Our results indicate that vortioxetine could be a potential osteoarthritis treatment (with better characteristics compared to duloxetine).",
publisher = "Elsevier Masson",
journal = "Biomedicine and Pharmacotherapy",
title = "The antidepressant drugs vortioxetine and duloxetine differentially and sex-dependently affect animal well-being, cognitive performance, cardiac redox status and histology in a model of osteoarthritis",
volume = "166",
doi = "10.1016/j.biopha.2023.115360"
}

Nastić, K., Pecikoza, U., Labudović-Borović, M., Kotur-Stevuljević, J., Micov, A., Jovanović, A., Tomić, M.,& Stepanović-Petrović, R.. (2023). The antidepressant drugs vortioxetine and duloxetine differentially and sex-dependently affect animal well-being, cognitive performance, cardiac redox status and histology in a model of osteoarthritis. in Biomedicine and Pharmacotherapy
Elsevier Masson., 166.
https://doi.org/10.1016/j.biopha.2023.115360

Nastić K, Pecikoza U, Labudović-Borović M, Kotur-Stevuljević J, Micov A, Jovanović A, Tomić M, Stepanović-Petrović R. The antidepressant drugs vortioxetine and duloxetine differentially and sex-dependently affect animal well-being, cognitive performance, cardiac redox status and histology in a model of osteoarthritis. in Biomedicine and Pharmacotherapy. 2023;166.
doi:10.1016/j.biopha.2023.115360 .

Nastić, Katarina, Pecikoza, Uroš, Labudović-Borović, Milica, Kotur-Stevuljević, Jelena, Micov, Ana, Jovanović, Aleksandar, Tomić, Maja, Stepanović-Petrović, Radica, "The antidepressant drugs vortioxetine and duloxetine differentially and sex-dependently affect animal well-being, cognitive performance, cardiac redox status and histology in a model of osteoarthritis" in Biomedicine and Pharmacotherapy, 166 (2023),
https://doi.org/10.1016/j.biopha.2023.115360 . .

TY  - CONF
AU  - Nastić, Katarina
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Jovanović, Aleksandar
AU  - Stepanović-Petrović, Radica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4525
AB  - Osteoarthritis is the most common rheumatic degenerative condition, with chronic
joint pain being the major source of disability. Currently, available treatment options for
alleviating pain are often ineffective and/or associated with unfavorable safety profiles (1).
Vortioxetine is a novel multimodal antidepressant, an inhibitor of serotonin reuptake, but
also an agonist, partial agonist, or antagonist of several serotonin (5-HT) receptors subtypes
involved in pain modulation (2). The study aimed to examine the efficacy of vortioxetine
compared to duloxetine, an antidepressant recommended for the treatment of osteoarthritis,
in the rat model of osteoarthritis. Osteoarthritis was induced by intra-articular injection of
monosodium iodoacetate (MIA; 2 mg/25 μL) in the right knee of male Wistar rats.
Vortioxetine/duloxetine was administered orally for 28 days following MIA injection. The
antinociceptive effect of vortioxetine/duloxetine was assessed using von Frey, acetone, and
weight-bearing test. The influence of treatments on animals’ well-being and motor
performance was examined in the burrowing and rotarod test, respectively. Vortioxetine (2
and 10 mg/kg) and duloxetine (15 and 25 mg/kg) significantly reduced mechanical and cold
allodynia, and improved weight borne on the ipsilateral hind paw in von Frey, acetone, and
weight-bearing test, respectively. Vortioxetine had no significant effect on burrowing
behavior, whereas duloxetine significantly reduced this inherent rodent activity. The rotarod
test did not demonstrate a significant effect of treatment on motor performance/sedation.
This study suggests comparable antinociceptive efficacy of vortioxetine with duloxetine, a
referent drug, as well as a better impact on the animals’ well-being of vortioxetine.
AB  - Osteoartritis predstavlja najčešće reumatsko degenerativno oboljenje, praćeno
hroničnim bolom, glavnim uzrokom onesposobljenosti pacijenata. Postojeće terapijske opcije
za otklanjanje bola su neretko nedovoljno efikasne i/ili udružene sa brojnim neželjenim
efektima (1). Vortioksetin je noviji antidepresiv multimodalnog mehanizma dejstva; inhibira
transporter za preuzimanje serotonina, a deluje i kao agonist, parcijalni agonist ili antagonist
različitih podtipova serotoninskih (5-HT) receptora uključenih u modulaciju bola (2). Cilj
ovog rada je bio ispitati efikasnost vortioksetina u poređenju sa duloksetinom,
antidepresivom preporučenim za lečenje osteoartritisa, u modelu osteoartritisa kod pacova.
Osteoartritis je indukovan intraartikularnom injekcijom natrijum-monojodacetata (MIA; 2
mg/25 μL) u desno koleno mužjaka pacova Wistar soja. Vortioksetin/duloksetin je
primenjivan oralno svakodnevno tokom 28 dana nakon injekcije MIA. Procena
antinociceptivne efikasnosti vortioksetina/duloksetina ispitivana je korišćenjem von Frey,
aceton testa i testa raspodele težine (eng. weight‐bearing). Uticaj tretmana na dobrobit
životinja (eng. well‐being), kao i motornu spretnost ispitivan je u testu kopanja i rotarod
testu, redom. Vortioksetin (2 i 10 mg/kg) i duloksetin (15 i 25 mg/kg) su značajno smanjili
mehaničku i hladnu alodiniju, i poboljšali oslanjanje životinja na ipsilateralnu šapu u von
Frey, aceton i testu raspodele težine, redom. Vortioksetin nije imao značajan uticaj na
aktivnost životinja u testu kopanja, dok je duloksetin značajno smanjio ovu inherentnu
aktivnost glodara. U rotarod testu nije pokazan značajan uticaj tretmana na motorne
performanse/sedaciju životinja. Ova studija je pokazala da su antinociceptivni efekti
vortioksetina i referentnog leka duloksetina uporedivi, kao i povoljniji uticaj vortioksetina
na opštu dobrobit životinja.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Efficacy of vortioxetine in the osteoarthritis rat model
T1  - Efikasnost vortioksetina u modelu osteoartritisa kod pacova
VL  - 72
IS  - 4 suplement
SP  - S245
EP  - S246
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4525
ER  - 

@conference{
author = "Nastić, Katarina and Pecikoza, Uroš and Micov, Ana and Tomić, Maja and Jovanović, Aleksandar and Stepanović-Petrović, Radica",
year = "2022",
abstract = "Osteoarthritis is the most common rheumatic degenerative condition, with chronic
joint pain being the major source of disability. Currently, available treatment options for
alleviating pain are often ineffective and/or associated with unfavorable safety profiles (1).
Vortioxetine is a novel multimodal antidepressant, an inhibitor of serotonin reuptake, but
also an agonist, partial agonist, or antagonist of several serotonin (5-HT) receptors subtypes
involved in pain modulation (2). The study aimed to examine the efficacy of vortioxetine
compared to duloxetine, an antidepressant recommended for the treatment of osteoarthritis,
in the rat model of osteoarthritis. Osteoarthritis was induced by intra-articular injection of
monosodium iodoacetate (MIA; 2 mg/25 μL) in the right knee of male Wistar rats.
Vortioxetine/duloxetine was administered orally for 28 days following MIA injection. The
antinociceptive effect of vortioxetine/duloxetine was assessed using von Frey, acetone, and
weight-bearing test. The influence of treatments on animals’ well-being and motor
performance was examined in the burrowing and rotarod test, respectively. Vortioxetine (2
and 10 mg/kg) and duloxetine (15 and 25 mg/kg) significantly reduced mechanical and cold
allodynia, and improved weight borne on the ipsilateral hind paw in von Frey, acetone, and
weight-bearing test, respectively. Vortioxetine had no significant effect on burrowing
behavior, whereas duloxetine significantly reduced this inherent rodent activity. The rotarod
test did not demonstrate a significant effect of treatment on motor performance/sedation.
This study suggests comparable antinociceptive efficacy of vortioxetine with duloxetine, a
referent drug, as well as a better impact on the animals’ well-being of vortioxetine., Osteoartritis predstavlja najčešće reumatsko degenerativno oboljenje, praćeno
hroničnim bolom, glavnim uzrokom onesposobljenosti pacijenata. Postojeće terapijske opcije
za otklanjanje bola su neretko nedovoljno efikasne i/ili udružene sa brojnim neželjenim
efektima (1). Vortioksetin je noviji antidepresiv multimodalnog mehanizma dejstva; inhibira
transporter za preuzimanje serotonina, a deluje i kao agonist, parcijalni agonist ili antagonist
različitih podtipova serotoninskih (5-HT) receptora uključenih u modulaciju bola (2). Cilj
ovog rada je bio ispitati efikasnost vortioksetina u poređenju sa duloksetinom,
antidepresivom preporučenim za lečenje osteoartritisa, u modelu osteoartritisa kod pacova.
Osteoartritis je indukovan intraartikularnom injekcijom natrijum-monojodacetata (MIA; 2
mg/25 μL) u desno koleno mužjaka pacova Wistar soja. Vortioksetin/duloksetin je
primenjivan oralno svakodnevno tokom 28 dana nakon injekcije MIA. Procena
antinociceptivne efikasnosti vortioksetina/duloksetina ispitivana je korišćenjem von Frey,
aceton testa i testa raspodele težine (eng. weight‐bearing). Uticaj tretmana na dobrobit
životinja (eng. well‐being), kao i motornu spretnost ispitivan je u testu kopanja i rotarod
testu, redom. Vortioksetin (2 i 10 mg/kg) i duloksetin (15 i 25 mg/kg) su značajno smanjili
mehaničku i hladnu alodiniju, i poboljšali oslanjanje životinja na ipsilateralnu šapu u von
Frey, aceton i testu raspodele težine, redom. Vortioksetin nije imao značajan uticaj na
aktivnost životinja u testu kopanja, dok je duloksetin značajno smanjio ovu inherentnu
aktivnost glodara. U rotarod testu nije pokazan značajan uticaj tretmana na motorne
performanse/sedaciju životinja. Ova studija je pokazala da su antinociceptivni efekti
vortioksetina i referentnog leka duloksetina uporedivi, kao i povoljniji uticaj vortioksetina
na opštu dobrobit životinja.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Efficacy of vortioxetine in the osteoarthritis rat model, Efikasnost vortioksetina u modelu osteoartritisa kod pacova",
volume = "72",
number = "4 suplement",
pages = "S245-S246",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4525"
}

Nastić, K., Pecikoza, U., Micov, A., Tomić, M., Jovanović, A.,& Stepanović-Petrović, R.. (2022). Efficacy of vortioxetine in the osteoarthritis rat model. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S245-S246.
https://hdl.handle.net/21.15107/rcub_farfar_4525

Nastić K, Pecikoza U, Micov A, Tomić M, Jovanović A, Stepanović-Petrović R. Efficacy of vortioxetine in the osteoarthritis rat model. in Arhiv za farmaciju. 2022;72(4 suplement):S245-S246.
https://hdl.handle.net/21.15107/rcub_farfar_4525 .

Nastić, Katarina, Pecikoza, Uroš, Micov, Ana, Tomić, Maja, Jovanović, Aleksandar, Stepanović-Petrović, Radica, "Efficacy of vortioxetine in the osteoarthritis rat model" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S245-S246,
https://hdl.handle.net/21.15107/rcub_farfar_4525 .

TY  - CONF
AU  - Stepanović-Petrović, Radica
AU  - Tomić, Maja
AU  - Jovanović, Aleksandar
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Nastić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4486
AB  - Osteoarthritis (OA) is the most common rheumatic disease, affecting over 300 million
people worldwide. It causes chronic pain, disability and is commonly associated with
comorbid diseases (CMD) that cause worse health outcomes, more complex management,
and increased healthcare costs. Current treatments (typical/atypical analgesics) have limited
efficacy and/or tolerability and usually do not affect or can even worse CMD. In era of longer
life expectancy, extended professional life and reduced pension funds in Serbia and Europe,
there is a compelling need for maintaining functionality and working capability of older
population. Our aim is to search for novel treatments that could concomitantly treat chronic
pain and its major CMD: depression, cognitive impairment and/or cardiovascular disease
(CVD). It was planned to test the effects of vortioxetine, a novel antidepressant with
multimodal mechanism of action, on pain, depressive and cognitive-impairment behaviour
and CV status in rat model of knee OA. Its effects will be compared to the effects of
duloxetine, the only antidepressant used for pain relief in OA. Next, we will test the effects of
2-component combinations of vortioxetine/duloxetine with adjuvant treatments (regular
exercise/metformin/nicotinamide), that showed the potential to alleviate pain, depression,
reduced cognition and/or CVD in preclinical/clinical research. If proved effective and well
tolerated, new treatment(s) could be implemented in clinical practice much faster and with
significantly less investment, than those required to develop brand new drug, as they consist
of drugs already approved for human use and safe, widely available and inexpensive non-
pharmacologic measures.
AB  - Osteoartritis (OA) je najčešć a reumatska bolest, koja pogađa preko 300 miliona ljudi
širom sveta. Prouzrokuje hronični bol, invaliditet i obično je povezan sa komorbiditetima koji
dovode do lošijih zdravstvenih ishoda, složenijeg lečenja i povećanja troškova zdravstvene
zaštite. Trenutno dostupne terapijske opcije (tipični/atipični analgetici) imaju ograničenu
efikasnost i/ili lošu podnošljivost, i obično ne utiču ili čak mogu pogoršati komorbiditete. U
vremenu kada su ljudski i radni vek produženi, a penzioni fondovi u Srbiji i Evropi smanjeni,
postoji velika potreba za održavanjem funkcionalnosti i radne sposobnosti starije populacije.
Naš cilj je da pronađemo nove terapijske opcije koje bi istovremeno mogle da leče hronični
bol i njegove glavne komorbiditete: depresiju, kognitivno oštećenje i/ili kardiovaskularne
bolesti (KVB). Planirano je ispitivanje efekata vortioksetina, novog antidepresiva sa
multimodalnim mehanizmom delovanja, na bol, depresivno ponašanje, kognitivno ošteć enje i
kardiovaskularni status pacova u modelu OA kolena. Efekti vortioksetina biće poređeni sa
efektima duloksetina, jedinog antidepresiva koji se koristi za ublažavanje bola kod OA. Zatim
će biti ispitani efekti dvokomponentnih kombinacija vortioksetina/duloksetina sa
adjuvantnim tretmanima (redovna fizička aktivnost/metformin/nikotinamid), koji su
pokazali efikasnost u ublažavanju bola, depresije, narušene kognicije i/ili KVB u
pretkliničkim/kliničkim istraživanjima. Ukoliko se pokaže da su efikasne i da se dobro
tolerišu, nove terapijske opcije bi se mogle implementirati u kliničku praksu mnogo brže i sa
znatno manje finansijskih ulaganja u poređenju sa vremenom i ulaganjima koja su potrebna
za razvoj novog leka, jer se sastoje od lekova koji su već odobreni za ljudsku upotrebu i
bezbednih, široko dostupnih i ekonomski povoljnih nefarmakoloških mera.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Multimodal control of chronic pain and comorbidities with atypical analgesics – “two birds with one stone”
T1  - Multimodalna kontrola hroničnog bola i komorbiditeta sa atipičnim analgeticima ‐,,više muva jednim udarcem“
VL  - 72
IS  - 4 suplement
SP  - S172
EP  - S173
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4486
ER  - 

@conference{
author = "Stepanović-Petrović, Radica and Tomić, Maja and Jovanović, Aleksandar and Pecikoza, Uroš and Micov, Ana and Nastić, Katarina",
year = "2022",
abstract = "Osteoarthritis (OA) is the most common rheumatic disease, affecting over 300 million
people worldwide. It causes chronic pain, disability and is commonly associated with
comorbid diseases (CMD) that cause worse health outcomes, more complex management,
and increased healthcare costs. Current treatments (typical/atypical analgesics) have limited
efficacy and/or tolerability and usually do not affect or can even worse CMD. In era of longer
life expectancy, extended professional life and reduced pension funds in Serbia and Europe,
there is a compelling need for maintaining functionality and working capability of older
population. Our aim is to search for novel treatments that could concomitantly treat chronic
pain and its major CMD: depression, cognitive impairment and/or cardiovascular disease
(CVD). It was planned to test the effects of vortioxetine, a novel antidepressant with
multimodal mechanism of action, on pain, depressive and cognitive-impairment behaviour
and CV status in rat model of knee OA. Its effects will be compared to the effects of
duloxetine, the only antidepressant used for pain relief in OA. Next, we will test the effects of
2-component combinations of vortioxetine/duloxetine with adjuvant treatments (regular
exercise/metformin/nicotinamide), that showed the potential to alleviate pain, depression,
reduced cognition and/or CVD in preclinical/clinical research. If proved effective and well
tolerated, new treatment(s) could be implemented in clinical practice much faster and with
significantly less investment, than those required to develop brand new drug, as they consist
of drugs already approved for human use and safe, widely available and inexpensive non-
pharmacologic measures., Osteoartritis (OA) je najčešć a reumatska bolest, koja pogađa preko 300 miliona ljudi
širom sveta. Prouzrokuje hronični bol, invaliditet i obično je povezan sa komorbiditetima koji
dovode do lošijih zdravstvenih ishoda, složenijeg lečenja i povećanja troškova zdravstvene
zaštite. Trenutno dostupne terapijske opcije (tipični/atipični analgetici) imaju ograničenu
efikasnost i/ili lošu podnošljivost, i obično ne utiču ili čak mogu pogoršati komorbiditete. U
vremenu kada su ljudski i radni vek produženi, a penzioni fondovi u Srbiji i Evropi smanjeni,
postoji velika potreba za održavanjem funkcionalnosti i radne sposobnosti starije populacije.
Naš cilj je da pronađemo nove terapijske opcije koje bi istovremeno mogle da leče hronični
bol i njegove glavne komorbiditete: depresiju, kognitivno oštećenje i/ili kardiovaskularne
bolesti (KVB). Planirano je ispitivanje efekata vortioksetina, novog antidepresiva sa
multimodalnim mehanizmom delovanja, na bol, depresivno ponašanje, kognitivno ošteć enje i
kardiovaskularni status pacova u modelu OA kolena. Efekti vortioksetina biće poređeni sa
efektima duloksetina, jedinog antidepresiva koji se koristi za ublažavanje bola kod OA. Zatim
će biti ispitani efekti dvokomponentnih kombinacija vortioksetina/duloksetina sa
adjuvantnim tretmanima (redovna fizička aktivnost/metformin/nikotinamid), koji su
pokazali efikasnost u ublažavanju bola, depresije, narušene kognicije i/ili KVB u
pretkliničkim/kliničkim istraživanjima. Ukoliko se pokaže da su efikasne i da se dobro
tolerišu, nove terapijske opcije bi se mogle implementirati u kliničku praksu mnogo brže i sa
znatno manje finansijskih ulaganja u poređenju sa vremenom i ulaganjima koja su potrebna
za razvoj novog leka, jer se sastoje od lekova koji su već odobreni za ljudsku upotrebu i
bezbednih, široko dostupnih i ekonomski povoljnih nefarmakoloških mera.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Multimodal control of chronic pain and comorbidities with atypical analgesics – “two birds with one stone”, Multimodalna kontrola hroničnog bola i komorbiditeta sa atipičnim analgeticima ‐,,više muva jednim udarcem“",
volume = "72",
number = "4 suplement",
pages = "S172-S173",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4486"
}

Stepanović-Petrović, R., Tomić, M., Jovanović, A., Pecikoza, U., Micov, A.,& Nastić, K.. (2022). Multimodal control of chronic pain and comorbidities with atypical analgesics – “two birds with one stone”. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S172-S173.
https://hdl.handle.net/21.15107/rcub_farfar_4486

Stepanović-Petrović R, Tomić M, Jovanović A, Pecikoza U, Micov A, Nastić K. Multimodal control of chronic pain and comorbidities with atypical analgesics – “two birds with one stone”. in Arhiv za farmaciju. 2022;72(4 suplement):S172-S173.
https://hdl.handle.net/21.15107/rcub_farfar_4486 .

Stepanović-Petrović, Radica, Tomić, Maja, Jovanović, Aleksandar, Pecikoza, Uroš, Micov, Ana, Nastić, Katarina, "Multimodal control of chronic pain and comorbidities with atypical analgesics – “two birds with one stone”" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S172-S173,
https://hdl.handle.net/21.15107/rcub_farfar_4486 .

TY  - JOUR
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Nastić, Katarina
AU  - Micov, Ana
AU  - Stepanović-Petrović, Radica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4253
AB  - Metformin (a widely used antidiabetic drug) has demonstrated efficacy in models of painful diabetic neuropathy
(PDN), as well as certain clinical efficacy in relieving/preventing PDN. This study aimed to determine the type of
interaction between metformin and duloxetine/oxycodone/eslicarbazepine acetate [ESL]/vitamin B12 in
relieving diabetic pain hypersensitivity. Antihyperalgesic efficacy was determined using a Von Frey apparatus in
mice with streptozotocin-induced PDN. We examined metformin’s efficacy following oral (acute and prolonged
7-day treatment) and local (spinal and peripheral) application. The examined analgesics were administered in a
single oral dose, whereas vitamin B12 was intraperitoneally administered for 7 days. In combination experiments,
metformin (prolonged treatment) and analgesics/vitamin B12 were co-administered in fixed-dose fractions of
their ED50 values and the type of interaction was determined using isobolographic analysis. Metformin produced
dose-dependent antihyperalgesic effects in diabetic mice after oral (acute and prolonged 7-day treatment) and
local spinal/peripheral application. Two-drug metformin combinations with analgesics/vitamin B12 also dose-
dependently reduced mechanical hyperalgesia. The isobolographic analysis revealed that metformin synergises
with analgesics/vitamin B12, with a 6–7 fold dose reduction of both drugs in the examined combinations. In
conclusion, metformin reduces hyperalgesia in diabetic animals, most likely by acting at the spinal and pe-
ripheral level. Additionally, it synergizes with duloxetine/oxycodone/ESL/vitamin B12 in reducing hyperalgesia.
Metformin co-treatment may increase analgesic efficacy and enable the use of lower (and potentially safer)
analgesic doses for treating PDN. Combined metformin-vitamin B12 use may provide more effective pain relief
and mitigate metformin-induced vitamin B12 deficiency.
PB  - Elsevier Masson s.r.l.
T2  - Biomedicine and Pharmacotherapy
T1  - Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy
VL  - 153
DO  - 10.1016/j.biopha.2022.113441
ER  - 

@article{
author = "Pecikoza, Uroš and Tomić, Maja and Nastić, Katarina and Micov, Ana and Stepanović-Petrović, Radica",
year = "2022",
abstract = "Metformin (a widely used antidiabetic drug) has demonstrated efficacy in models of painful diabetic neuropathy
(PDN), as well as certain clinical efficacy in relieving/preventing PDN. This study aimed to determine the type of
interaction between metformin and duloxetine/oxycodone/eslicarbazepine acetate [ESL]/vitamin B12 in
relieving diabetic pain hypersensitivity. Antihyperalgesic efficacy was determined using a Von Frey apparatus in
mice with streptozotocin-induced PDN. We examined metformin’s efficacy following oral (acute and prolonged
7-day treatment) and local (spinal and peripheral) application. The examined analgesics were administered in a
single oral dose, whereas vitamin B12 was intraperitoneally administered for 7 days. In combination experiments,
metformin (prolonged treatment) and analgesics/vitamin B12 were co-administered in fixed-dose fractions of
their ED50 values and the type of interaction was determined using isobolographic analysis. Metformin produced
dose-dependent antihyperalgesic effects in diabetic mice after oral (acute and prolonged 7-day treatment) and
local spinal/peripheral application. Two-drug metformin combinations with analgesics/vitamin B12 also dose-
dependently reduced mechanical hyperalgesia. The isobolographic analysis revealed that metformin synergises
with analgesics/vitamin B12, with a 6–7 fold dose reduction of both drugs in the examined combinations. In
conclusion, metformin reduces hyperalgesia in diabetic animals, most likely by acting at the spinal and pe-
ripheral level. Additionally, it synergizes with duloxetine/oxycodone/ESL/vitamin B12 in reducing hyperalgesia.
Metformin co-treatment may increase analgesic efficacy and enable the use of lower (and potentially safer)
analgesic doses for treating PDN. Combined metformin-vitamin B12 use may provide more effective pain relief
and mitigate metformin-induced vitamin B12 deficiency.",
publisher = "Elsevier Masson s.r.l.",
journal = "Biomedicine and Pharmacotherapy",
title = "Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy",
volume = "153",
doi = "10.1016/j.biopha.2022.113441"
}

Pecikoza, U., Tomić, M., Nastić, K., Micov, A.,& Stepanović-Petrović, R.. (2022). Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy. in Biomedicine and Pharmacotherapy
Elsevier Masson s.r.l.., 153.
https://doi.org/10.1016/j.biopha.2022.113441

Pecikoza U, Tomić M, Nastić K, Micov A, Stepanović-Petrović R. Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy. in Biomedicine and Pharmacotherapy. 2022;153.
doi:10.1016/j.biopha.2022.113441 .

Pecikoza, Uroš, Tomić, Maja, Nastić, Katarina, Micov, Ana, Stepanović-Petrović, Radica, "Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy" in Biomedicine and Pharmacotherapy, 153 (2022),
https://doi.org/10.1016/j.biopha.2022.113441 . .

TY  - CONF
AU  - Lasica, Anđelka
AU  - Tomić, Maja
AU  - Nastić, Katarina
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Stepanović-Petrović, Radica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4578
AB  - Metformin, a well-known antidiabetic drug, has been shown to possess analgesic
properties in inflammatory pain models, but the mechanisms of its antinociceptive effects
are not completely understood (1,2). We aimed to examine the involvement of serotonergic
mechanisms in metformin-induced antinociception in a model of inflammatory pain, using
the formalin test in mice. Firstly, we examined the antinociceptive effects of intraperitoneally
administered metformin in the first and second phase of the test. Then, the involvement of
serotonergic receptors was evaluated by intraperitoneally pretreating mice with a 5-HT1B/1D
(GR127935) or 5-HT1A receptor antagonist (WAY100635). Further, we examined the effect of
metformin after depletion of endogenous serotonin with a tryptophan-hydroxylase inhibitor
(PCPA; applied intraperitoneally for 4 days). Additionally, to avoid misinterpretation of
motor incoordination, we performed the rotarod test with the highest tested metformin
dose. Metformin (50-200 mg/kg) produced significant and dose-dependent antinociceptive
effects (17-81%) in the second (inflammatory) phase of the test. Pretreatment with
antagonists significantly reduced the antinociceptive effect of metformin (150 mg/kg).
GR127935 inhibited the effects of metformin by 67% (1 mg/kg) and 100% (3 mg/kg),
whereas the inhibitory effects for WAY100635 were 19% (1 mg/kg) and 68% (3 mg/kg).
Depletion of serotonin with PCPA (100 mg/kg/day) significantly reduced the antinociceptive
effects of higher metformin doses (150 and 200 mg/kg). Metformin (200 mg/kg) had no
influence on rotarod performance. This study demonstrates that 5-HT1B/1D and 5-HT1A
receptors are involved in metformin’s antinociceptive effects and that metformin’s action on
these receptors seems to be indirect (mediated by endogenous serotonin released by
metformin).
AB  - Metformin je dobro poznat antidijabetik, za koji je pokazano da poseduje analgetička
svojstva u modelima inflamatornog bola. Međutim, mehanizmi njegovog antinociceptivnog
dejstva nisu u potpunosti rasvetljeni (1,2). Cilj ovog rada je bio ispitati učešće
serotonergičkih mehanizama u antinociceptivnom dejstvu metformina u inflamatornom
modelu bola – korišćenjem formalinskog testa kod miševa. Inicijalno su ispitani
antinociceptivni efekti metformina, nakon intraperitonealne primene, u prvoj i drugoj fazi
testa. Uključenost serotoninskih receptora je procenjena nakon intraperitonealne primene
antagonista 5-HT 1B/1D (GR127935) ili 5-HT1A (WAY100635) receptora. U nastavku
eksperimenata, efekat metformina je ispitan nakon deplecije endogenog serotonina,
primenom inhibitora triptofan-hidroksilaze (PCPA; primenjen intraperitonealno tokom 4
dana). Dodatno, efekat najveće testirane doze metformina je ispitan u rotarod testu, kako bi
se isključila mogućnost pogrešnog tumačenja motorne inkoordinacije. Metformin (50-200
mg/kg) je pokazao značajno i dozno-zavisno antinociceptivno dejstvo (17-81%) u drugoj
(inflamatornoj) fazi testa. Primena antagonista je značajno smanjila antinociceptivni efekat
metformina (150 mg/kg). GR127935 je inhibirao efekte metformina za 67% (1 mg/kg) i
100% (3 mg/kg), dok su inhibitorni efekti WAY100635 bili 19% (1 mg/kg) i 68% (3 mg/kg).
Deplecija serotonina korišćenjem PCPA (100 mg/kg/dan) je značajno smanjila
antinociceptivne efekte metformina primenjenog u većim dozama (150 i 200 mg/kg).
Metformin (200 mg/kg) nije imao značajan uticaj na performanse miševa u rotarod testu.
Ova studija je pokazala uključenost 5-HT1B/1D i 5-HT1A receptora u antinociceptivnom dejstvu
metformina, koje je verovatno posledica indirektnog uticaja leka na receptore (posredstvom
oslobađanja endogenog serotonina od strane metformina).
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - The involvement of serotonergic mechanisms in the antinociceptive effect of metformin
T1  - Učešće serotonergičkih mehanizama u antinociceptivnom dejstvu metformina
VL  - 72
IS  - 4 suplement
SP  - S448
EP  - S449
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4578
ER  - 

@conference{
author = "Lasica, Anđelka and Tomić, Maja and Nastić, Katarina and Pecikoza, Uroš and Micov, Ana and Stepanović-Petrović, Radica",
year = "2022",
abstract = "Metformin, a well-known antidiabetic drug, has been shown to possess analgesic
properties in inflammatory pain models, but the mechanisms of its antinociceptive effects
are not completely understood (1,2). We aimed to examine the involvement of serotonergic
mechanisms in metformin-induced antinociception in a model of inflammatory pain, using
the formalin test in mice. Firstly, we examined the antinociceptive effects of intraperitoneally
administered metformin in the first and second phase of the test. Then, the involvement of
serotonergic receptors was evaluated by intraperitoneally pretreating mice with a 5-HT1B/1D
(GR127935) or 5-HT1A receptor antagonist (WAY100635). Further, we examined the effect of
metformin after depletion of endogenous serotonin with a tryptophan-hydroxylase inhibitor
(PCPA; applied intraperitoneally for 4 days). Additionally, to avoid misinterpretation of
motor incoordination, we performed the rotarod test with the highest tested metformin
dose. Metformin (50-200 mg/kg) produced significant and dose-dependent antinociceptive
effects (17-81%) in the second (inflammatory) phase of the test. Pretreatment with
antagonists significantly reduced the antinociceptive effect of metformin (150 mg/kg).
GR127935 inhibited the effects of metformin by 67% (1 mg/kg) and 100% (3 mg/kg),
whereas the inhibitory effects for WAY100635 were 19% (1 mg/kg) and 68% (3 mg/kg).
Depletion of serotonin with PCPA (100 mg/kg/day) significantly reduced the antinociceptive
effects of higher metformin doses (150 and 200 mg/kg). Metformin (200 mg/kg) had no
influence on rotarod performance. This study demonstrates that 5-HT1B/1D and 5-HT1A
receptors are involved in metformin’s antinociceptive effects and that metformin’s action on
these receptors seems to be indirect (mediated by endogenous serotonin released by
metformin)., Metformin je dobro poznat antidijabetik, za koji je pokazano da poseduje analgetička
svojstva u modelima inflamatornog bola. Međutim, mehanizmi njegovog antinociceptivnog
dejstva nisu u potpunosti rasvetljeni (1,2). Cilj ovog rada je bio ispitati učešće
serotonergičkih mehanizama u antinociceptivnom dejstvu metformina u inflamatornom
modelu bola – korišćenjem formalinskog testa kod miševa. Inicijalno su ispitani
antinociceptivni efekti metformina, nakon intraperitonealne primene, u prvoj i drugoj fazi
testa. Uključenost serotoninskih receptora je procenjena nakon intraperitonealne primene
antagonista 5-HT 1B/1D (GR127935) ili 5-HT1A (WAY100635) receptora. U nastavku
eksperimenata, efekat metformina je ispitan nakon deplecije endogenog serotonina,
primenom inhibitora triptofan-hidroksilaze (PCPA; primenjen intraperitonealno tokom 4
dana). Dodatno, efekat najveće testirane doze metformina je ispitan u rotarod testu, kako bi
se isključila mogućnost pogrešnog tumačenja motorne inkoordinacije. Metformin (50-200
mg/kg) je pokazao značajno i dozno-zavisno antinociceptivno dejstvo (17-81%) u drugoj
(inflamatornoj) fazi testa. Primena antagonista je značajno smanjila antinociceptivni efekat
metformina (150 mg/kg). GR127935 je inhibirao efekte metformina za 67% (1 mg/kg) i
100% (3 mg/kg), dok su inhibitorni efekti WAY100635 bili 19% (1 mg/kg) i 68% (3 mg/kg).
Deplecija serotonina korišćenjem PCPA (100 mg/kg/dan) je značajno smanjila
antinociceptivne efekte metformina primenjenog u većim dozama (150 i 200 mg/kg).
Metformin (200 mg/kg) nije imao značajan uticaj na performanse miševa u rotarod testu.
Ova studija je pokazala uključenost 5-HT1B/1D i 5-HT1A receptora u antinociceptivnom dejstvu
metformina, koje je verovatno posledica indirektnog uticaja leka na receptore (posredstvom
oslobađanja endogenog serotonina od strane metformina).",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "The involvement of serotonergic mechanisms in the antinociceptive effect of metformin, Učešće serotonergičkih mehanizama u antinociceptivnom dejstvu metformina",
volume = "72",
number = "4 suplement",
pages = "S448-S449",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4578"
}

Lasica, A., Tomić, M., Nastić, K., Pecikoza, U., Micov, A.,& Stepanović-Petrović, R.. (2022). The involvement of serotonergic mechanisms in the antinociceptive effect of metformin. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S448-S449.
https://hdl.handle.net/21.15107/rcub_farfar_4578

Lasica A, Tomić M, Nastić K, Pecikoza U, Micov A, Stepanović-Petrović R. The involvement of serotonergic mechanisms in the antinociceptive effect of metformin. in Arhiv za farmaciju. 2022;72(4 suplement):S448-S449.
https://hdl.handle.net/21.15107/rcub_farfar_4578 .

Lasica, Anđelka, Tomić, Maja, Nastić, Katarina, Pecikoza, Uroš, Micov, Ana, Stepanović-Petrović, Radica, "The involvement of serotonergic mechanisms in the antinociceptive effect of metformin" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S448-S449,
https://hdl.handle.net/21.15107/rcub_farfar_4578 .

TY  - CONF
AU  - Pecikoza, Uroš
AU  - Lasica, Anđelka
AU  - Tomić, Maja
AU  - Micov, Ana
AU  - Nastić, Katarina
AU  - Stepanović-Petrović, Radica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4577
AB  - Several lines of (pre)clinical evidence have emerged that the antidiabetic drug
metformin can alleviate inflammatory/neuropathic pain (1). Although the mechanism is not
completely understood, there are reports that metformin can affect neurotransmitters
involved in pain modulation, such as its ability to increase peripheral serotonin release (2).
Here, we evaluated metformin’s efficacy following local peripheral administration in an
inflammatory pain model and examined the potential involvement of serotonin receptors.
We used the formalin test in mice, where we measured duration of nociceptive behavior in
the first and second phase of the test. First, we examined the metformin’s antinociceptive
effects following intraplantar administration. Additionally, the highest tested metformin
dose was applied contralateral to the formalin-injected side, to exclude possible systemic
effects. In the second part, we evaluated the effects of a 5-HT1A (WAY100635) and 5-HT1B/1D
antagonist (GR127935) on the antinociceptive effects of a fixed, effective dose of metformin
(antagonists were co-administered intraplantarly with metformin). Metformin (0.1-2
mg/paw) produced significant and dose-dependent antinociceptive effects (32-72%) in the
second (inflammatory) phase. Contralateral application of metformin (2 mg/paw) had no
significant antinociceptive effects. Both antagonists significantly reduced the antinociceptive
effects of metformin (1 mg/paw). The levels of inhibition of metformin’s antinociceptive
effect produced by WAY100635 were 56% (5 μg/paw) and 82% (7.5 μg/paw), whereas
GR127935 inhibited metformin’s efficacy by 24% (3.75 μg/paw) and 80% (5 μg/paw). This
study demonstrates that peripheral metformin application can produce antinociceptive
effects against inflammatory pain and that activation of peripheral 5-HT 1A and 5-HT1B/1D
receptors contributes to these effects.
AB  - Postoje brojni dokazi iz (pre)kliničkih studija da metformin, lek iz grupe
antidijabetika, može ublažiti inflamatorni/neuropatski bol (1). Iako mehanizam dejstva nije
u potpunosti razjašnjen, podaci ukazuju da metformin može uticati na neurotransmitere
uključene u modulaciju bola, poput sposobnosti da poveća oslobađanje serotonina na
periferiji (2). U ovom radu je ispitana efikasnost metformina nakon lokalne periferne
primene u modelu inflamatornog bola, kao i potencijalna uključenost serotoninskih
receptora. Korišćen je formalinski test kod miševa, u kome je mereno vreme provedeno u
nociceptivnom ponašanju, u prvoj i drugoj fazi testa. Prvo su ispitani antinociceptivni efekti
metformina nakon intraplantarne primene. Dodatno, najveća testirana doza metformina je
primenjena kontralateralno u odnosu na mesto injektovanja formalina, kako bi se isključili
mogući sistemski efekti. U drugom delu studije, ispitani su efekti antagoniste 5-HT 1A
(WAY100635) i 5-HT1B/1D (GR127935) receptora na antinociceptivno dejstvo fiksne,
efektivne doze metformina (antagonisti su primenjeni intraplantarno, istovremeno sa
metforminom). Metformin (0,1-2 mg/šapi) je ispoljio značajan i dozno-zavisan
antinociceptivni efekat (32-72%) u drugoj (inflamatornoj) fazi testa. Kontralateralna
primena metformina (2 mg/šapi) nije imala značajan antinociceptivni efekat. Primenjeni
antagonisti su značajno smanjili antinociceptivne efekte metformina (1 mg/šapi). Stepeni
inhibicije antinociceptivnog dejstva metformina koje je postigao WAY100635 su bili 56% (5
μg/šapi) i 82% (7,5 μg/šapi), dok je GR127935 inhibirao efikasnost metformina za 24%
(3,75 μg/šapi) i 80% (5 μg/šapi). Ova studija je pokazala da periferna primena metformina
proizvodi antinociceptivni efekat kod inflamatornog bola i da aktivacija perifernih 5-HT1A i 5-
HT1B/1D receptora doprinosi ovom efektu.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Activation of peripheral serotonin 5-HT1A and 5-HT1B/1D receptors contributes to the antinociceptive properties of metformin
T1  - Aktivacija perifernih serotoninskih 5‐HT1A i 5‐HT 1B/1D receptora doprinosi antinociceptivnom dejstvu metformina
VL  - 72
IS  - 4 suplement
SP  - S446
EP  - S447
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4577
ER  - 

@conference{
author = "Pecikoza, Uroš and Lasica, Anđelka and Tomić, Maja and Micov, Ana and Nastić, Katarina and Stepanović-Petrović, Radica",
year = "2022",
abstract = "Several lines of (pre)clinical evidence have emerged that the antidiabetic drug
metformin can alleviate inflammatory/neuropathic pain (1). Although the mechanism is not
completely understood, there are reports that metformin can affect neurotransmitters
involved in pain modulation, such as its ability to increase peripheral serotonin release (2).
Here, we evaluated metformin’s efficacy following local peripheral administration in an
inflammatory pain model and examined the potential involvement of serotonin receptors.
We used the formalin test in mice, where we measured duration of nociceptive behavior in
the first and second phase of the test. First, we examined the metformin’s antinociceptive
effects following intraplantar administration. Additionally, the highest tested metformin
dose was applied contralateral to the formalin-injected side, to exclude possible systemic
effects. In the second part, we evaluated the effects of a 5-HT1A (WAY100635) and 5-HT1B/1D
antagonist (GR127935) on the antinociceptive effects of a fixed, effective dose of metformin
(antagonists were co-administered intraplantarly with metformin). Metformin (0.1-2
mg/paw) produced significant and dose-dependent antinociceptive effects (32-72%) in the
second (inflammatory) phase. Contralateral application of metformin (2 mg/paw) had no
significant antinociceptive effects. Both antagonists significantly reduced the antinociceptive
effects of metformin (1 mg/paw). The levels of inhibition of metformin’s antinociceptive
effect produced by WAY100635 were 56% (5 μg/paw) and 82% (7.5 μg/paw), whereas
GR127935 inhibited metformin’s efficacy by 24% (3.75 μg/paw) and 80% (5 μg/paw). This
study demonstrates that peripheral metformin application can produce antinociceptive
effects against inflammatory pain and that activation of peripheral 5-HT 1A and 5-HT1B/1D
receptors contributes to these effects., Postoje brojni dokazi iz (pre)kliničkih studija da metformin, lek iz grupe
antidijabetika, može ublažiti inflamatorni/neuropatski bol (1). Iako mehanizam dejstva nije
u potpunosti razjašnjen, podaci ukazuju da metformin može uticati na neurotransmitere
uključene u modulaciju bola, poput sposobnosti da poveća oslobađanje serotonina na
periferiji (2). U ovom radu je ispitana efikasnost metformina nakon lokalne periferne
primene u modelu inflamatornog bola, kao i potencijalna uključenost serotoninskih
receptora. Korišćen je formalinski test kod miševa, u kome je mereno vreme provedeno u
nociceptivnom ponašanju, u prvoj i drugoj fazi testa. Prvo su ispitani antinociceptivni efekti
metformina nakon intraplantarne primene. Dodatno, najveća testirana doza metformina je
primenjena kontralateralno u odnosu na mesto injektovanja formalina, kako bi se isključili
mogući sistemski efekti. U drugom delu studije, ispitani su efekti antagoniste 5-HT 1A
(WAY100635) i 5-HT1B/1D (GR127935) receptora na antinociceptivno dejstvo fiksne,
efektivne doze metformina (antagonisti su primenjeni intraplantarno, istovremeno sa
metforminom). Metformin (0,1-2 mg/šapi) je ispoljio značajan i dozno-zavisan
antinociceptivni efekat (32-72%) u drugoj (inflamatornoj) fazi testa. Kontralateralna
primena metformina (2 mg/šapi) nije imala značajan antinociceptivni efekat. Primenjeni
antagonisti su značajno smanjili antinociceptivne efekte metformina (1 mg/šapi). Stepeni
inhibicije antinociceptivnog dejstva metformina koje je postigao WAY100635 su bili 56% (5
μg/šapi) i 82% (7,5 μg/šapi), dok je GR127935 inhibirao efikasnost metformina za 24%
(3,75 μg/šapi) i 80% (5 μg/šapi). Ova studija je pokazala da periferna primena metformina
proizvodi antinociceptivni efekat kod inflamatornog bola i da aktivacija perifernih 5-HT1A i 5-
HT1B/1D receptora doprinosi ovom efektu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Activation of peripheral serotonin 5-HT1A and 5-HT1B/1D receptors contributes to the antinociceptive properties of metformin, Aktivacija perifernih serotoninskih 5‐HT1A i 5‐HT 1B/1D receptora doprinosi antinociceptivnom dejstvu metformina",
volume = "72",
number = "4 suplement",
pages = "S446-S447",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4577"
}

Pecikoza, U., Lasica, A., Tomić, M., Micov, A., Nastić, K.,& Stepanović-Petrović, R.. (2022). Activation of peripheral serotonin 5-HT1A and 5-HT1B/1D receptors contributes to the antinociceptive properties of metformin. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S446-S447.
https://hdl.handle.net/21.15107/rcub_farfar_4577

Pecikoza U, Lasica A, Tomić M, Micov A, Nastić K, Stepanović-Petrović R. Activation of peripheral serotonin 5-HT1A and 5-HT1B/1D receptors contributes to the antinociceptive properties of metformin. in Arhiv za farmaciju. 2022;72(4 suplement):S446-S447.
https://hdl.handle.net/21.15107/rcub_farfar_4577 .

Pecikoza, Uroš, Lasica, Anđelka, Tomić, Maja, Micov, Ana, Nastić, Katarina, Stepanović-Petrović, Radica, "Activation of peripheral serotonin 5-HT1A and 5-HT1B/1D receptors contributes to the antinociceptive properties of metformin" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S446-S447,
https://hdl.handle.net/21.15107/rcub_farfar_4577 .

TY  - JOUR
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4257
AB  - In the pediatric population, acute respiratory tract infections (RTIs) are the most
common reason for seeking professional help from a physician or a pharmacist.
Alleviation of symptoms is the only therapeutic measure in viral RTIs and is an adjunct
to antibiotic therapy in bacterial RTIs. This article discusses pharmacologic and non-
pharmacologic options for treating nasal congestion, cough, fever and sore throat in RTIs
and clinical evidence on their efficacy and safety in the pediatric population. In general,
clinical studies conducted in children for most of these drug groups are few or
nonexistent, making it difficult to create evidence-based recommendations. Nasal
decongestants, cough suppressants, mucolytics, expectorants, antipyretics/analgesics and
sore throat local preparations are available in suitable pharmaceutical forms and strengths
for the certain age. As many of them are over-the-counter (OTC) preparations, it is
necessary to strictly take into account the age of the child in whom they may be used and
dose properly. Multicomponent preparations carry the risk of taking unnecessary
medications and of their side effects. The use of multiple OTC medicines is associated
with the risk of an overdose of a component that may be present in different preparations.
Appropriate non-pharmacological measures (e.g. oral hydration, nasal saline application
or irrigation, honey) may be helpful and should be used whenever possible due to their
safety.
AB  - U pedijatrijskoj populaciji, akutne infekcije respiratornog trakta (IRT) su najčešći razlog traženja stručne pomoći od lekara ili farmaceuta. Ublažavanje simptoma je jedina terapijska mera kod virusnih i dodatak je antibiotskoj terapiji kod bakterijskih IRT. Ovaj članak govori o farmakološkim i nefarmakološkim opcijama za lečenje nazalne kongestije, kašlja, povišene telesne temperature i upale grla kod IRT i kliničkim dokazima o njihovoj efikasnosti i bezbednosti u pedijatrijskoj populaciji. Uopšteno govoreći, kliničke studije sprovedene kod dece za većinu ovih grupa lekova su malobrojne ili ih uopšte nema, što otežava pripremu preporuka zasnovanih na dokazima. Dostupni su nazalni dekongestivi, antitusici, mukolitici, ekspektoransi, antipiretici/analgetici i lokalni preparati za ublažavanje simptoma upale grla, u odgovarajućim farmaceutskim oblicima i jačinama za određeni uzrast. Kako se mnogi od njih izdaju bez lekarskog recepta (OTC), potrebno je striktno voditi računa o uzrastu deteta u kome se smeju koristiti i pravilnom doziranju. Višekomponentni preparati nose rizik od primene nepotrebnih lekova i njihovih neželjenih efekata. Primena više OTC lekova nosi rizik od predoziranja komponente koja može biti sastojak različitih preparata. Odgovarajuće nefarmakološke mere (npr. oralna hidratacija, primena fiziološkog rastvora u nos ili ispiranje nosa, med) mogu biti od pomoći i treba ih koristiti kad god je to moguće zbog njihove bezbednosti.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Medications and non-pharmacological measures to alleviate the symptoms of respiratory tract infections in the pediatric population
T1  - Lekovi i nefarmakološke mere za ublažavanje simptoma infekcija respiratornog trakta u pedijatrijskoj populaciji
VL  - 72
IS  - 3
SP  - 300
EP  - 319
DO  - 10.5937/arhfarm72-38025
ER  - 

@article{
author = "Tomić, Maja and Pecikoza, Uroš",
year = "2022",
abstract = "In the pediatric population, acute respiratory tract infections (RTIs) are the most
common reason for seeking professional help from a physician or a pharmacist.
Alleviation of symptoms is the only therapeutic measure in viral RTIs and is an adjunct
to antibiotic therapy in bacterial RTIs. This article discusses pharmacologic and non-
pharmacologic options for treating nasal congestion, cough, fever and sore throat in RTIs
and clinical evidence on their efficacy and safety in the pediatric population. In general,
clinical studies conducted in children for most of these drug groups are few or
nonexistent, making it difficult to create evidence-based recommendations. Nasal
decongestants, cough suppressants, mucolytics, expectorants, antipyretics/analgesics and
sore throat local preparations are available in suitable pharmaceutical forms and strengths
for the certain age. As many of them are over-the-counter (OTC) preparations, it is
necessary to strictly take into account the age of the child in whom they may be used and
dose properly. Multicomponent preparations carry the risk of taking unnecessary
medications and of their side effects. The use of multiple OTC medicines is associated
with the risk of an overdose of a component that may be present in different preparations.
Appropriate non-pharmacological measures (e.g. oral hydration, nasal saline application
or irrigation, honey) may be helpful and should be used whenever possible due to their
safety., U pedijatrijskoj populaciji, akutne infekcije respiratornog trakta (IRT) su najčešći razlog traženja stručne pomoći od lekara ili farmaceuta. Ublažavanje simptoma je jedina terapijska mera kod virusnih i dodatak je antibiotskoj terapiji kod bakterijskih IRT. Ovaj članak govori o farmakološkim i nefarmakološkim opcijama za lečenje nazalne kongestije, kašlja, povišene telesne temperature i upale grla kod IRT i kliničkim dokazima o njihovoj efikasnosti i bezbednosti u pedijatrijskoj populaciji. Uopšteno govoreći, kliničke studije sprovedene kod dece za većinu ovih grupa lekova su malobrojne ili ih uopšte nema, što otežava pripremu preporuka zasnovanih na dokazima. Dostupni su nazalni dekongestivi, antitusici, mukolitici, ekspektoransi, antipiretici/analgetici i lokalni preparati za ublažavanje simptoma upale grla, u odgovarajućim farmaceutskim oblicima i jačinama za određeni uzrast. Kako se mnogi od njih izdaju bez lekarskog recepta (OTC), potrebno je striktno voditi računa o uzrastu deteta u kome se smeju koristiti i pravilnom doziranju. Višekomponentni preparati nose rizik od primene nepotrebnih lekova i njihovih neželjenih efekata. Primena više OTC lekova nosi rizik od predoziranja komponente koja može biti sastojak različitih preparata. Odgovarajuće nefarmakološke mere (npr. oralna hidratacija, primena fiziološkog rastvora u nos ili ispiranje nosa, med) mogu biti od pomoći i treba ih koristiti kad god je to moguće zbog njihove bezbednosti.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Medications and non-pharmacological measures to alleviate the symptoms of respiratory tract infections in the pediatric population, Lekovi i nefarmakološke mere za ublažavanje simptoma infekcija respiratornog trakta u pedijatrijskoj populaciji",
volume = "72",
number = "3",
pages = "300-319",
doi = "10.5937/arhfarm72-38025"
}

Tomić, M.,& Pecikoza, U.. (2022). Medications and non-pharmacological measures to alleviate the symptoms of respiratory tract infections in the pediatric population. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 72(3), 300-319.
https://doi.org/10.5937/arhfarm72-38025

Tomić M, Pecikoza U. Medications and non-pharmacological measures to alleviate the symptoms of respiratory tract infections in the pediatric population. in Arhiv za farmaciju. 2022;72(3):300-319.
doi:10.5937/arhfarm72-38025 .

Tomić, Maja, Pecikoza, Uroš, "Medications and non-pharmacological measures to alleviate the symptoms of respiratory tract infections in the pediatric population" in Arhiv za farmaciju, 72, no. 3 (2022):300-319,
https://doi.org/10.5937/arhfarm72-38025 . .

TY  - JOUR
AU  - Pecikoza, Uroš
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4399
AB  - Functional thyroid disorders (hypothyroidism and hyperthyroidism) are amongst the most
common endocrine disorders pharmacists encounter on a daily basis. They are highly prevalent
in iodine-replete areas, and affect women about 10 times more often than man. Hypothyroidism
(thyroid hormone deficiency) is usually caused by Hashimoto’s thyroiditis, an autoimmune
disorder that leads to gradual thyroid destruction. The drug-of-choice for treating hypothyroidism
is levothyroxine, a synthetic form of thyroxine. Key points which need to be discussed with
patients who are prescribed levothyroxine for the first time are when/how to administer this drug,
how its effects are monitored, what drugs may affect its efficacy, and the importance of properly
treating hypothyroidism during pregnancy. Hyperthyroidism (increased production of thyroid
hormones) is most often caused by Graves’ disease, another thyroid autoimmune disorder in
which stimulatory autoantibodies against the TSH receptor lead to increased thyroid function.
Graves’ disease is most commonly treated with thionamide drugs (thiamazole, carbimazole or
propylthiouracil) and patients using these drugs should be advised on the monitoring
requirements, duration of treatment, and how to recognize possible serious adverse effects
(agranulocytosis and hepatotoxicity), and informed that these drugs must be used during
pregnancy in order to reduce the risk of adverse outcomes for the mother and baby.
AB  - Funkcionalni poremećaji štitaste žlezde (hipotiroidizam i hipertiroidizam) spadaju u najčešće endokrine poremećaje sa kojima se farmaceuti svakodnevno susreću. Ovi poremećaji su veoma prevalentni u područjima sa adekvatnim unosom joda i pogađaju žene oko 10 puta češće nego muškarce. Hipotiroidizam (nedostatak tiroidnih hormona) je obično posledica Hašimotovog tiroiditisa, autoimunskog poremećaja koji dovodi do postepene destrukcije štitaste žlezde. Lek izbora za lečenje hipotiroidizma je levotiroksin, sintetski oblik hormona tiroksina. Ključne tačke o kojima treba razgovarati sa pacijentima kojima je prvi put propisan levotiroksin su kada/kako da se primeni ovaj lek, kako se prate njegovi efekti, koji lekovi mogu uticati na njegovu efikasnost i važnost pravilnog lečenja hipotiroidizma tokom trudnoće. Hipertiroidizam (povećana proizvodnja tiroidnih hormona) najčešće je uzrokovan Grejvsovom bolešću, još jednim autoimunskim poremećajem štitaste žlezde, u kojem stimulatorna autoantitela na TSH receptore dovode do povećane funkcije štitaste žlezde. Grejvsova bolest se najčešće leči tioamidima (tiamazol, karbimazol, propiltiouracil), a pacijenti koji koriste ove lekove treba da budu obavešteni o načinu praćenja efikasnosti, trajanju lečenja, kako da prepoznaju moguće ozbiljne neželjene efekte (agranulocitozu i hepatotoksičnost), kao i da se ovi lekovi moraju koristiti tokom trudnoće kako bi se smanjio rizik od štetnih ishoda za majku i bebu.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Functional thyroid disorders in the pharmacy setting – how can we help our patients?
T1  - Funkcionalni poremećaji štitaste žlezde u farmaceutskoj praksi - kako možemo pomoći našim pacijentima?
VL  - 72
IS  - 5
SP  - 503
EP  - 520
DO  - 10.5937/arhfarm72-39858
ER  - 

@article{
author = "Pecikoza, Uroš",
year = "2022",
abstract = "Functional thyroid disorders (hypothyroidism and hyperthyroidism) are amongst the most
common endocrine disorders pharmacists encounter on a daily basis. They are highly prevalent
in iodine-replete areas, and affect women about 10 times more often than man. Hypothyroidism
(thyroid hormone deficiency) is usually caused by Hashimoto’s thyroiditis, an autoimmune
disorder that leads to gradual thyroid destruction. The drug-of-choice for treating hypothyroidism
is levothyroxine, a synthetic form of thyroxine. Key points which need to be discussed with
patients who are prescribed levothyroxine for the first time are when/how to administer this drug,
how its effects are monitored, what drugs may affect its efficacy, and the importance of properly
treating hypothyroidism during pregnancy. Hyperthyroidism (increased production of thyroid
hormones) is most often caused by Graves’ disease, another thyroid autoimmune disorder in
which stimulatory autoantibodies against the TSH receptor lead to increased thyroid function.
Graves’ disease is most commonly treated with thionamide drugs (thiamazole, carbimazole or
propylthiouracil) and patients using these drugs should be advised on the monitoring
requirements, duration of treatment, and how to recognize possible serious adverse effects
(agranulocytosis and hepatotoxicity), and informed that these drugs must be used during
pregnancy in order to reduce the risk of adverse outcomes for the mother and baby., Funkcionalni poremećaji štitaste žlezde (hipotiroidizam i hipertiroidizam) spadaju u najčešće endokrine poremećaje sa kojima se farmaceuti svakodnevno susreću. Ovi poremećaji su veoma prevalentni u područjima sa adekvatnim unosom joda i pogađaju žene oko 10 puta češće nego muškarce. Hipotiroidizam (nedostatak tiroidnih hormona) je obično posledica Hašimotovog tiroiditisa, autoimunskog poremećaja koji dovodi do postepene destrukcije štitaste žlezde. Lek izbora za lečenje hipotiroidizma je levotiroksin, sintetski oblik hormona tiroksina. Ključne tačke o kojima treba razgovarati sa pacijentima kojima je prvi put propisan levotiroksin su kada/kako da se primeni ovaj lek, kako se prate njegovi efekti, koji lekovi mogu uticati na njegovu efikasnost i važnost pravilnog lečenja hipotiroidizma tokom trudnoće. Hipertiroidizam (povećana proizvodnja tiroidnih hormona) najčešće je uzrokovan Grejvsovom bolešću, još jednim autoimunskim poremećajem štitaste žlezde, u kojem stimulatorna autoantitela na TSH receptore dovode do povećane funkcije štitaste žlezde. Grejvsova bolest se najčešće leči tioamidima (tiamazol, karbimazol, propiltiouracil), a pacijenti koji koriste ove lekove treba da budu obavešteni o načinu praćenja efikasnosti, trajanju lečenja, kako da prepoznaju moguće ozbiljne neželjene efekte (agranulocitozu i hepatotoksičnost), kao i da se ovi lekovi moraju koristiti tokom trudnoće kako bi se smanjio rizik od štetnih ishoda za majku i bebu.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Functional thyroid disorders in the pharmacy setting – how can we help our patients?, Funkcionalni poremećaji štitaste žlezde u farmaceutskoj praksi - kako možemo pomoći našim pacijentima?",
volume = "72",
number = "5",
pages = "503-520",
doi = "10.5937/arhfarm72-39858"
}

Pecikoza, U.. (2022). Functional thyroid disorders in the pharmacy setting – how can we help our patients?. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 72(5), 503-520.
https://doi.org/10.5937/arhfarm72-39858

Pecikoza U. Functional thyroid disorders in the pharmacy setting – how can we help our patients?. in Arhiv za farmaciju. 2022;72(5):503-520.
doi:10.5937/arhfarm72-39858 .

Pecikoza, Uroš, "Functional thyroid disorders in the pharmacy setting – how can we help our patients?" in Arhiv za farmaciju, 72, no. 5 (2022):503-520,
https://doi.org/10.5937/arhfarm72-39858 . .

TY  - CONF
AU  - Pecikoza, Uroš
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4467
AB  - Migraine is one of the most common neurological diseases and about 20% of patients
suffer from frequent episodic or chronic forms of the disease, which represent a significant
global cause of chronic disability. Despite its high prevalence, the pathophysiology of
migraine is still not completely understood. However, it has been known for several decades
that the development of migraine attacks is dependent on the calcitonin gene-related peptide
(CGRP), a neuropeptide that modulates nociceptive signaling within neuronal pathways
important for migraine pain. Drugs that reduce the effects of CGRP (CGRP antagonists) have
recently become available and include small-molecule CGRP-receptor antagonists (so-called
gepants) that are approved for acute treatment and/or prevention of migraine attacks
(ubrogepant, atogepant, rimegepant), as well as monoclonal antibodies, which are approved
for prevention of migraine attacks (anti-CGRP antibodies: fremanezumab, galcanezumab,
eptinezumab; anti-CGRP receptor antibody: erenumab). The effectiveness of gepants in
alleviating migraine attacks is somewhat lower compared to triptans (standard drugs for
treating migraine attacks), but gepants are considered safer than triptans with regard to
cardiovascular side effects and the risk of medication-overuse headache. Monoclonal anti-
CGRP antibodies have been shown to be useful drugs for patients who have not responded to
standard prophylactic therapy (e.g., β-blockers or antiepileptics), but their high cost limits
widespread use. Although the effectiveness of CGRP antagonists has been unequivocally
proven, it will take time to precisely define the role of these drugs in modern migraine
pharmacotherapy, and it is especially important to examine the safety of their long-term use.
AB  - Migrena spada u najčešća neurološka oboljenja i oko 20% pacijenata ima čestu
epizodičnu ili hroničnu formu bolesti, koje predstavljaju značajan uzrok hronične
onesposobljenosti na globalnom nivou. Uprkos visokoj prevalenciji, patofiziologija migrene
je još uvek nedovoljno razjašnjena. Međutim, već nekoliko decenija je poznato da u nastanku
napada migrene veliku ulogu igra peptid srodan kalcitoninu (engl. calcitonine gene related
peptide – CGRP), neuropeptid koji moduliše nociceptivnu signalizaciju u okviru neuronskih
puteva značajnih za nastanak migrenoznog bola. Lekovi koji smanjuju efekte CGRP-a (CGRP
antagonisti) su nedavno postali dostupni i obuhvataju antagoniste CGRP-receptora male
molekulske mase (tzv. gepanti) koji su odobreni za akutni tretman i/ili prevenciju napada
migrene (ubrogepant, atogepant, rimegepant), kao i monoklonska antitela koja su odobrena
za prevenciju napada (anti-CGRP antitela: fremanezumab, galkanezumab, eptinezumab; anti-
CGRP receptorsko antitelo: erenumab). Efikasnost gepanta u ublažavanju napada migrene je
nešto niža u poređenju sa triptanima (standardnim lekovima za tretman napada), međutim
smatra se da su gepanti bezbedniji od triptana u pogledu kardiovaskularnih neželjenih
efekata i rizika od izazivanja glavobolje prekomerne upotrebe analgetika. Monoklonska anti-
CGRP antitela su se pokazala kao korisni lekovi za pacijente koji nisu odgovorili na
standardnu profilaktičku terapiju (npr. β-blokatorima ili antiepilepticima), međutim visoka
cena ograničava njihovu širu upotrebu. Iako je efikasnost CGRP antagonista nesumnjivo
dokazana, za precizno definisanje uloge ovih lekova u savremenoj farmakoterapiji migrene
će biti potrebno vreme, a posebno značajno je ispitati bezbednost njihove dugoročne
primene.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - CGRP antagonists and the treatment of migraine – new heroes against an old enemy
T1  - CGRP antagonisti i terapija migrene – novi heroji protiv starog neprijatelja
VL  - 72
IS  - 4 suplement
SP  - S126
EP  - S127
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4467
ER  - 

@conference{
author = "Pecikoza, Uroš",
year = "2022",
abstract = "Migraine is one of the most common neurological diseases and about 20% of patients
suffer from frequent episodic or chronic forms of the disease, which represent a significant
global cause of chronic disability. Despite its high prevalence, the pathophysiology of
migraine is still not completely understood. However, it has been known for several decades
that the development of migraine attacks is dependent on the calcitonin gene-related peptide
(CGRP), a neuropeptide that modulates nociceptive signaling within neuronal pathways
important for migraine pain. Drugs that reduce the effects of CGRP (CGRP antagonists) have
recently become available and include small-molecule CGRP-receptor antagonists (so-called
gepants) that are approved for acute treatment and/or prevention of migraine attacks
(ubrogepant, atogepant, rimegepant), as well as monoclonal antibodies, which are approved
for prevention of migraine attacks (anti-CGRP antibodies: fremanezumab, galcanezumab,
eptinezumab; anti-CGRP receptor antibody: erenumab). The effectiveness of gepants in
alleviating migraine attacks is somewhat lower compared to triptans (standard drugs for
treating migraine attacks), but gepants are considered safer than triptans with regard to
cardiovascular side effects and the risk of medication-overuse headache. Monoclonal anti-
CGRP antibodies have been shown to be useful drugs for patients who have not responded to
standard prophylactic therapy (e.g., β-blockers or antiepileptics), but their high cost limits
widespread use. Although the effectiveness of CGRP antagonists has been unequivocally
proven, it will take time to precisely define the role of these drugs in modern migraine
pharmacotherapy, and it is especially important to examine the safety of their long-term use., Migrena spada u najčešća neurološka oboljenja i oko 20% pacijenata ima čestu
epizodičnu ili hroničnu formu bolesti, koje predstavljaju značajan uzrok hronične
onesposobljenosti na globalnom nivou. Uprkos visokoj prevalenciji, patofiziologija migrene
je još uvek nedovoljno razjašnjena. Međutim, već nekoliko decenija je poznato da u nastanku
napada migrene veliku ulogu igra peptid srodan kalcitoninu (engl. calcitonine gene related
peptide – CGRP), neuropeptid koji moduliše nociceptivnu signalizaciju u okviru neuronskih
puteva značajnih za nastanak migrenoznog bola. Lekovi koji smanjuju efekte CGRP-a (CGRP
antagonisti) su nedavno postali dostupni i obuhvataju antagoniste CGRP-receptora male
molekulske mase (tzv. gepanti) koji su odobreni za akutni tretman i/ili prevenciju napada
migrene (ubrogepant, atogepant, rimegepant), kao i monoklonska antitela koja su odobrena
za prevenciju napada (anti-CGRP antitela: fremanezumab, galkanezumab, eptinezumab; anti-
CGRP receptorsko antitelo: erenumab). Efikasnost gepanta u ublažavanju napada migrene je
nešto niža u poređenju sa triptanima (standardnim lekovima za tretman napada), međutim
smatra se da su gepanti bezbedniji od triptana u pogledu kardiovaskularnih neželjenih
efekata i rizika od izazivanja glavobolje prekomerne upotrebe analgetika. Monoklonska anti-
CGRP antitela su se pokazala kao korisni lekovi za pacijente koji nisu odgovorili na
standardnu profilaktičku terapiju (npr. β-blokatorima ili antiepilepticima), međutim visoka
cena ograničava njihovu širu upotrebu. Iako je efikasnost CGRP antagonista nesumnjivo
dokazana, za precizno definisanje uloge ovih lekova u savremenoj farmakoterapiji migrene
će biti potrebno vreme, a posebno značajno je ispitati bezbednost njihove dugoročne
primene.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "CGRP antagonists and the treatment of migraine – new heroes against an old enemy, CGRP antagonisti i terapija migrene – novi heroji protiv starog neprijatelja",
volume = "72",
number = "4 suplement",
pages = "S126-S127",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4467"
}

Pecikoza, U.. (2022). CGRP antagonists and the treatment of migraine – new heroes against an old enemy. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S126-S127.
https://hdl.handle.net/21.15107/rcub_farfar_4467

Pecikoza U. CGRP antagonists and the treatment of migraine – new heroes against an old enemy. in Arhiv za farmaciju. 2022;72(4 suplement):S126-S127.
https://hdl.handle.net/21.15107/rcub_farfar_4467 .

Pecikoza, Uroš, "CGRP antagonists and the treatment of migraine – new heroes against an old enemy" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S126-S127,
https://hdl.handle.net/21.15107/rcub_farfar_4467 .

TY  - JOUR
AU  - Milutinović, Violeta
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
AU  - Niketić, Marjan
AU  - Ušjak, Ljuboš
AU  - Petrović, Silvana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3641
AB  - Present study investigated triterpene profile, antihyperalgesic and antiedematous activities of Hieracium scheppigianum flowering aerial parts dichloromethane extract (SCH), and antihyperalgesic and antiedematous activities of previously chemically characterised polyphenol-rich H. glabratum and H. calophyllum flowering aerial parts methanol extracts (GLA and CAL, respectively). α- and β-Amyrin and their acetates, and lupeol acetate were identified and quantified in SCH by GC-FID and GC-MS. In carrageenan-induced localised inflammation model in rats, SCH and GLA (50–200 mg/kg, p.o.) produced significant and dose-dependent antihyperalgesic effect of 26.9%–56.2% (ED50=163.0 ± 26.5 mg/kg) and 25.3%–51.6% (ED50=211.6 ± 70.6 mg/kg), respectively, and CAL (200 mg/kg, p.o.) exhibited effect of 38.1%. Extracts did not significantly reduce paw edema. SCH and GLA, which demonstrated higher (over 50%) antihyperalgesic efficacy, were tested in a rotarod test (200 mg/kg, p.o.) and no alteration of motor coordination was observed. Also, acute administration of SCH and GLA in mice (2000 mg/kg, p.o.) caused neither mortality nor toxicity.
PB  - Taylor & Francis Ltd
T2  - Natural Product Research
T1  - Investigation of antihyperalgesic and antiedematous activities of three Hieracium species
VL  - 35
IS  - 23
SP  - 5384
EP  - 5388
DO  - 10.1080/14786419.2020.1768086
ER  - 

@article{
author = "Milutinović, Violeta and Pecikoza, Uroš and Tomić, Maja and Stepanović-Petrović, Radica and Niketić, Marjan and Ušjak, Ljuboš and Petrović, Silvana",
year = "2021",
abstract = "Present study investigated triterpene profile, antihyperalgesic and antiedematous activities of Hieracium scheppigianum flowering aerial parts dichloromethane extract (SCH), and antihyperalgesic and antiedematous activities of previously chemically characterised polyphenol-rich H. glabratum and H. calophyllum flowering aerial parts methanol extracts (GLA and CAL, respectively). α- and β-Amyrin and their acetates, and lupeol acetate were identified and quantified in SCH by GC-FID and GC-MS. In carrageenan-induced localised inflammation model in rats, SCH and GLA (50–200 mg/kg, p.o.) produced significant and dose-dependent antihyperalgesic effect of 26.9%–56.2% (ED50=163.0 ± 26.5 mg/kg) and 25.3%–51.6% (ED50=211.6 ± 70.6 mg/kg), respectively, and CAL (200 mg/kg, p.o.) exhibited effect of 38.1%. Extracts did not significantly reduce paw edema. SCH and GLA, which demonstrated higher (over 50%) antihyperalgesic efficacy, were tested in a rotarod test (200 mg/kg, p.o.) and no alteration of motor coordination was observed. Also, acute administration of SCH and GLA in mice (2000 mg/kg, p.o.) caused neither mortality nor toxicity.",
publisher = "Taylor & Francis Ltd",
journal = "Natural Product Research",
title = "Investigation of antihyperalgesic and antiedematous activities of three Hieracium species",
volume = "35",
number = "23",
pages = "5384-5388",
doi = "10.1080/14786419.2020.1768086"
}

Milutinović, V., Pecikoza, U., Tomić, M., Stepanović-Petrović, R., Niketić, M., Ušjak, L.,& Petrović, S.. (2021). Investigation of antihyperalgesic and antiedematous activities of three Hieracium species. in Natural Product Research
Taylor & Francis Ltd., 35(23), 5384-5388.
https://doi.org/10.1080/14786419.2020.1768086

Milutinović V, Pecikoza U, Tomić M, Stepanović-Petrović R, Niketić M, Ušjak L, Petrović S. Investigation of antihyperalgesic and antiedematous activities of three Hieracium species. in Natural Product Research. 2021;35(23):5384-5388.
doi:10.1080/14786419.2020.1768086 .

Milutinović, Violeta, Pecikoza, Uroš, Tomić, Maja, Stepanović-Petrović, Radica, Niketić, Marjan, Ušjak, Ljuboš, Petrović, Silvana, "Investigation of antihyperalgesic and antiedematous activities of three Hieracium species" in Natural Product Research, 35, no. 23 (2021):5384-5388,
https://doi.org/10.1080/14786419.2020.1768086 . .

TY  - JOUR
AU  - Todorović, Marija
AU  - Micov, Ana
AU  - Nastić, Katarina
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Vuković, Milja
AU  - Stepanović-Petrović, Radica
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4009
AB  - Vortioxetine is a novel atypical antidepressant with multimodal activity that has recently demonstrated efficacy against neuropathic pain. There is no published data about its analgesic properties in models characterized by peripheral inflammation and consequent pain pathway sensitization, nor data on its mechanism of antinociceptive action. This study aimed to investigate vortioxetine's antinociceptive/antihyperalgesic effects in trigeminal, visceral, and somatic inflammatory pain models, and provide evidence on its mechanism of action in the modulation of trigeminal nociception. Vortioxetine's effects on the nociceptive behavior in orofacial formalin test (OFT) and acetic acid-writhing test in mice and on mechanical hyperalgesia in carrageenan-induced paw inflammation in rats were examined following peroral single administration. The involvement of serotonergic/adrenergic/cholinergic/cannabinoid/adenosine receptors was evaluated in OFT by intraperitoneally treating mice with an appropriate antagonist immediately after vortioxetine application. We used antagonists of 5-HT1B/1D serotonergic (GR 127935), α1-adrenergic (prazosin), α2-adrenergic (yohimbine), β1-adrenergic (metoprolol), muscarinic (atropine), α7 nicotinic (methyllycaconitine), CB1/CB2 cannabinoid (AM251 and AM630), and adenosine A1 (DPCPX) receptors. Vortioxetine dose-dependently reduced pain behavior in OFT and acetic acid writhing test, as well as inflammatory hyperalgesia in paw pressure test. All examined antagonists except prazosin dose-dependently inhibited vortioxetine's antinociceptive effects. In conclusion, vortioxetine exerted analgesic efficacy in trigeminal, visceral, and somatic inflammatory pain. The effect is at least in part mediated by 5-HT1B/1D serotonergic, α2/β1-adrenergic, muscarinic and nicotinic cholinergic, CB1/CB2 cannabinoid, and adenosine A1 receptors. These findings contribute to better understanding of the analgesic effect of vortioxetine and suggest its potential usefulness for inflammatory pain treatment.
PB  - John Wiley and Sons Inc
T2  - Fundamental and Clinical Pharmacology
T1  - Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action
VL  - 36
IS  - 2
SP  - 237
EP  - 249
DO  - 10.1111/fcp.12737
ER  - 

@article{
author = "Todorović, Marija and Micov, Ana and Nastić, Katarina and Tomić, Maja and Pecikoza, Uroš and Vuković, Milja and Stepanović-Petrović, Radica",
year = "2021",
abstract = "Vortioxetine is a novel atypical antidepressant with multimodal activity that has recently demonstrated efficacy against neuropathic pain. There is no published data about its analgesic properties in models characterized by peripheral inflammation and consequent pain pathway sensitization, nor data on its mechanism of antinociceptive action. This study aimed to investigate vortioxetine's antinociceptive/antihyperalgesic effects in trigeminal, visceral, and somatic inflammatory pain models, and provide evidence on its mechanism of action in the modulation of trigeminal nociception. Vortioxetine's effects on the nociceptive behavior in orofacial formalin test (OFT) and acetic acid-writhing test in mice and on mechanical hyperalgesia in carrageenan-induced paw inflammation in rats were examined following peroral single administration. The involvement of serotonergic/adrenergic/cholinergic/cannabinoid/adenosine receptors was evaluated in OFT by intraperitoneally treating mice with an appropriate antagonist immediately after vortioxetine application. We used antagonists of 5-HT1B/1D serotonergic (GR 127935), α1-adrenergic (prazosin), α2-adrenergic (yohimbine), β1-adrenergic (metoprolol), muscarinic (atropine), α7 nicotinic (methyllycaconitine), CB1/CB2 cannabinoid (AM251 and AM630), and adenosine A1 (DPCPX) receptors. Vortioxetine dose-dependently reduced pain behavior in OFT and acetic acid writhing test, as well as inflammatory hyperalgesia in paw pressure test. All examined antagonists except prazosin dose-dependently inhibited vortioxetine's antinociceptive effects. In conclusion, vortioxetine exerted analgesic efficacy in trigeminal, visceral, and somatic inflammatory pain. The effect is at least in part mediated by 5-HT1B/1D serotonergic, α2/β1-adrenergic, muscarinic and nicotinic cholinergic, CB1/CB2 cannabinoid, and adenosine A1 receptors. These findings contribute to better understanding of the analgesic effect of vortioxetine and suggest its potential usefulness for inflammatory pain treatment.",
publisher = "John Wiley and Sons Inc",
journal = "Fundamental and Clinical Pharmacology",
title = "Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action",
volume = "36",
number = "2",
pages = "237-249",
doi = "10.1111/fcp.12737"
}

Todorović, M., Micov, A., Nastić, K., Tomić, M., Pecikoza, U., Vuković, M.,& Stepanović-Petrović, R.. (2021). Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action. in Fundamental and Clinical Pharmacology
John Wiley and Sons Inc., 36(2), 237-249.
https://doi.org/10.1111/fcp.12737

Todorović M, Micov A, Nastić K, Tomić M, Pecikoza U, Vuković M, Stepanović-Petrović R. Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action. in Fundamental and Clinical Pharmacology. 2021;36(2):237-249.
doi:10.1111/fcp.12737 .

Todorović, Marija, Micov, Ana, Nastić, Katarina, Tomić, Maja, Pecikoza, Uroš, Vuković, Milja, Stepanović-Petrović, Radica, "Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action" in Fundamental and Clinical Pharmacology, 36, no. 2 (2021):237-249,
https://doi.org/10.1111/fcp.12737 . .

TY  - THES
AU  - Pecikoza, Uroš
PY  - 2021
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=8244
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:23972/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=39014921
UR  - https://nardus.mpn.gov.rs/handle/123456789/18520
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4037
AB  - Bol je kompleksno senzorno iskustvo koje ima jasnu zaštitnu ulogu, ali pod određenim uslovima može da postane hronično stanje koje značajno narušava kvalitet života. Postojeći analgetici, iako nesumnjivo korisni u terapiji različitih bolnih stanja, neretko su nedovoljno efikasni ili bezbedni. Zato postoji potreba za razvojem novih ili otkrivanjem efikasnih kombinacija postojećih analgetika kako bi se poboljšala terapija bola.Ciljevi ovog rada su bili ispitivanje efekata, mehanizama dejstva i interakcija dva potencijalna alternativna analgetika, antiepileptika eslikarbazepin acetata (ESL) i antidijabetika metformina u modelima inflamatornog i neuropatskog bola.Efekti ESL i metformina su ispitani u modelima inflamatornog trigeminalnog, visceralnog i somatskog bola, kao i modelu bolne dijabetesne neuropatije. Mehanizmi dejstva ESL u modelu trigeminalnog bola su ispitani farmakološkim pristupom, korišćenjem antagonista receptora značajnih za modulaciju bola. Vrsta interakcije između ESL/metformina i analgetika u modelima inflamatornog i neuropatskog bola je utvrđena izobolografskom analizom.ESL i metformin su pokazali efikasnost u svim korišćenim modelima inflamatornog bola i u modelu bolne dijabetesne neuropatije. Utvrđeno je da ESL ublažava trigeminalni bol posredstvom serotoninskih 5-HT1B/1D, α2/β1-adrenergičkih, muskarinskih, CB1/CB2 kanabinoidnih i opioidnih receptora. ESL i metformin stupaju u aditivne ili sinergističke interakcije sa različitim analgeticima u modelima inflamatornog i neuropatskog bola.Efikasnost ESL i metformina u modelima bola bi mogla da ukaže na njihovu potencijalnu kliničku primenu kao analgetika. Dodatno, poznavanje mehanizama dejstva ESL može doprineti uspešnoj primeni ovog leka u terapiji bola. Na kraju, oba leka stupaju u povoljne interakcije sa postojećim analgeticima. Ovaj nalaz ukazuje na potencijalno bolju efikasnost i/ili bezbednost kombinovane u odnosu na monoterapiju, kao i koji analgetici bi mogli biti povoljan izbor za lečenje bola kod ljudi koji već primenjuju ESL/metformin zbog komorbiditeta.
AB  - Pain is a complex sensory experience, which has a clear protective role, but under certain circumstances pain can become a chronic condition that significantly impairs the quality of life. Existing analgesics, although undoubtedly useful in the treatment of various painful conditions, are often insufficiently effective or safe. Therefore, there is a need to develop new drugs or to discover effective combinations of existing drugs in order to improve pain therapy.The objectives of this study were to investigate the effects, mechanisms of action, and interactions of two potential alternative analgesics, the antiepileptic eslicarbazepine acetate (ESL) and the antidiabetic metformin in models of inflammatory and neuropathic pain.The effects of ESL and metformin were examined in models of inflammatory trigeminal, visceral and somatic pain, as well as in a model of painful diabetic neuropathy. The mechanisms of action of ESL in the model of trigeminal pain were examined by a pharmacological approach, using antagonists of different receptors important for pain modulation. The type of interaction between ESL/metformin and analgesics in models of inflammatory and neuropathic pain was determined using isobolographic analysis.ESL and metformin were effective in all models of inflammatory pain that were used, as well as in the model of painful diabetic neuropathy. ESL was found to relieve trigeminal pain by activating serotonin 5-HT1B/1D, α2/β1-adrenergic, muscarinic, CB1/CB2 cannabinoid and opioid receptors. ESL and metformin interacted in an additive or synergistic manner with different analgesics in models of inflammatory and neuropathic pain.The efficacy of ESL and metformin in pain models may indicate their potential clinical application as analgesics. In addition, knowledge of the mechanisms of action of ESL may contribute to the successful use of this drug in the treatment of pain. Finally, both drugs interact favorably with existing analgesics. This finding indicates potentially better efficacy and/or safety of combination therapy compared to monotherapy, as well as which analgesics could be a favorable choice for the treatment of pain in people already using ESL/metformin due to comorbidities.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola
UR  - https://hdl.handle.net/21.15107/rcub_nardus_18520
ER  - 

@phdthesis{
author = "Pecikoza, Uroš",
year = "2021",
abstract = "Bol je kompleksno senzorno iskustvo koje ima jasnu zaštitnu ulogu, ali pod određenim uslovima može da postane hronično stanje koje značajno narušava kvalitet života. Postojeći analgetici, iako nesumnjivo korisni u terapiji različitih bolnih stanja, neretko su nedovoljno efikasni ili bezbedni. Zato postoji potreba za razvojem novih ili otkrivanjem efikasnih kombinacija postojećih analgetika kako bi se poboljšala terapija bola.Ciljevi ovog rada su bili ispitivanje efekata, mehanizama dejstva i interakcija dva potencijalna alternativna analgetika, antiepileptika eslikarbazepin acetata (ESL) i antidijabetika metformina u modelima inflamatornog i neuropatskog bola.Efekti ESL i metformina su ispitani u modelima inflamatornog trigeminalnog, visceralnog i somatskog bola, kao i modelu bolne dijabetesne neuropatije. Mehanizmi dejstva ESL u modelu trigeminalnog bola su ispitani farmakološkim pristupom, korišćenjem antagonista receptora značajnih za modulaciju bola. Vrsta interakcije između ESL/metformina i analgetika u modelima inflamatornog i neuropatskog bola je utvrđena izobolografskom analizom.ESL i metformin su pokazali efikasnost u svim korišćenim modelima inflamatornog bola i u modelu bolne dijabetesne neuropatije. Utvrđeno je da ESL ublažava trigeminalni bol posredstvom serotoninskih 5-HT1B/1D, α2/β1-adrenergičkih, muskarinskih, CB1/CB2 kanabinoidnih i opioidnih receptora. ESL i metformin stupaju u aditivne ili sinergističke interakcije sa različitim analgeticima u modelima inflamatornog i neuropatskog bola.Efikasnost ESL i metformina u modelima bola bi mogla da ukaže na njihovu potencijalnu kliničku primenu kao analgetika. Dodatno, poznavanje mehanizama dejstva ESL može doprineti uspešnoj primeni ovog leka u terapiji bola. Na kraju, oba leka stupaju u povoljne interakcije sa postojećim analgeticima. Ovaj nalaz ukazuje na potencijalno bolju efikasnost i/ili bezbednost kombinovane u odnosu na monoterapiju, kao i koji analgetici bi mogli biti povoljan izbor za lečenje bola kod ljudi koji već primenjuju ESL/metformin zbog komorbiditeta., Pain is a complex sensory experience, which has a clear protective role, but under certain circumstances pain can become a chronic condition that significantly impairs the quality of life. Existing analgesics, although undoubtedly useful in the treatment of various painful conditions, are often insufficiently effective or safe. Therefore, there is a need to develop new drugs or to discover effective combinations of existing drugs in order to improve pain therapy.The objectives of this study were to investigate the effects, mechanisms of action, and interactions of two potential alternative analgesics, the antiepileptic eslicarbazepine acetate (ESL) and the antidiabetic metformin in models of inflammatory and neuropathic pain.The effects of ESL and metformin were examined in models of inflammatory trigeminal, visceral and somatic pain, as well as in a model of painful diabetic neuropathy. The mechanisms of action of ESL in the model of trigeminal pain were examined by a pharmacological approach, using antagonists of different receptors important for pain modulation. The type of interaction between ESL/metformin and analgesics in models of inflammatory and neuropathic pain was determined using isobolographic analysis.ESL and metformin were effective in all models of inflammatory pain that were used, as well as in the model of painful diabetic neuropathy. ESL was found to relieve trigeminal pain by activating serotonin 5-HT1B/1D, α2/β1-adrenergic, muscarinic, CB1/CB2 cannabinoid and opioid receptors. ESL and metformin interacted in an additive or synergistic manner with different analgesics in models of inflammatory and neuropathic pain.The efficacy of ESL and metformin in pain models may indicate their potential clinical application as analgesics. In addition, knowledge of the mechanisms of action of ESL may contribute to the successful use of this drug in the treatment of pain. Finally, both drugs interact favorably with existing analgesics. This finding indicates potentially better efficacy and/or safety of combination therapy compared to monotherapy, as well as which analgesics could be a favorable choice for the treatment of pain in people already using ESL/metformin due to comorbidities.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola",
url = "https://hdl.handle.net/21.15107/rcub_nardus_18520"
}

Pecikoza, U.. (2021). Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_18520

Pecikoza U. Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola. in Универзитет у Београду. 2021;.
https://hdl.handle.net/21.15107/rcub_nardus_18520 .

Pecikoza, Uroš, "Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola" in Универзитет у Београду (2021),
https://hdl.handle.net/21.15107/rcub_nardus_18520 .

TY  - JOUR
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Todorović, Marija B.
AU  - Vuković, Milja
AU  - Pecikoza, Uroš
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena D.
AU  - Stepanović-Petrović, Radica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3600
AB  - Chronic pain and depression commonly occur together so dual-acting agents might be particularly useful. The population of patients with chemotherapy-induced neuropathy is increasing in parallel with the increase of population of cancer survivors and there is a compelling need for satisfactory treatment of symptoms of neuropathy and concomitant depression. We examined the effects of vortioxetine, a novel antidepressant with unique mechanism of action, on pain hypersensitivity and depression-like behavior in oxaliplatin-induced neuropathy model in mice (OIPN). Vortioxetine (1–10 mg/kg, p.o.) significantly and dose-dependently reduced mechanical allodynia in von Frey test and cold allodynia in acetone test in OIPN mice, in both repeated prophylactic and acute therapeutic treatment regimens. It also reduced depression-like behavior in the forced swimming test in OIPN mice, in both treatment paradigms. Its antiallodynic and antidepressive-like effects were comparable to those exerted by duloxetine (1–15 mg/kg, p.o.). The antiallodynic and antidepressive-like effects of repeatedly administered vortioxetine might be related to the increased content of 5-hydroxytryptamine (5- HT) and noradrenaline (NA), detected in the brainstem of treated OIPN mice. These results indicate that vortioxetine could be potentially useful in prevention and treatment of chemotherapy-induced neuropathy, for the relief of pain and concomitant depressive symptoms. It should be further tested to this regard in clinical settings.
PB  - Elsevier
T2  - Progress in Neuro-Psychopharmacology and Biological Psychiatry
T1  - Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy
VL  - 103
DO  - 10.1016/j.pnpbp.2020.109975
ER  - 

@article{
author = "Micov, Ana and Tomić, Maja and Todorović, Marija B. and Vuković, Milja and Pecikoza, Uroš and Jasnić, Nebojša and Đorđević, Jelena D. and Stepanović-Petrović, Radica",
year = "2020",
abstract = "Chronic pain and depression commonly occur together so dual-acting agents might be particularly useful. The population of patients with chemotherapy-induced neuropathy is increasing in parallel with the increase of population of cancer survivors and there is a compelling need for satisfactory treatment of symptoms of neuropathy and concomitant depression. We examined the effects of vortioxetine, a novel antidepressant with unique mechanism of action, on pain hypersensitivity and depression-like behavior in oxaliplatin-induced neuropathy model in mice (OIPN). Vortioxetine (1–10 mg/kg, p.o.) significantly and dose-dependently reduced mechanical allodynia in von Frey test and cold allodynia in acetone test in OIPN mice, in both repeated prophylactic and acute therapeutic treatment regimens. It also reduced depression-like behavior in the forced swimming test in OIPN mice, in both treatment paradigms. Its antiallodynic and antidepressive-like effects were comparable to those exerted by duloxetine (1–15 mg/kg, p.o.). The antiallodynic and antidepressive-like effects of repeatedly administered vortioxetine might be related to the increased content of 5-hydroxytryptamine (5- HT) and noradrenaline (NA), detected in the brainstem of treated OIPN mice. These results indicate that vortioxetine could be potentially useful in prevention and treatment of chemotherapy-induced neuropathy, for the relief of pain and concomitant depressive symptoms. It should be further tested to this regard in clinical settings.",
publisher = "Elsevier",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
title = "Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy",
volume = "103",
doi = "10.1016/j.pnpbp.2020.109975"
}

Micov, A., Tomić, M., Todorović, M. B., Vuković, M., Pecikoza, U., Jasnić, N., Đorđević, J. D.,& Stepanović-Petrović, R.. (2020). Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy. in Progress in Neuro-Psychopharmacology and Biological Psychiatry
Elsevier., 103.
https://doi.org/10.1016/j.pnpbp.2020.109975

Micov A, Tomić M, Todorović MB, Vuković M, Pecikoza U, Jasnić N, Đorđević JD, Stepanović-Petrović R. Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy. in Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2020;103.
doi:10.1016/j.pnpbp.2020.109975 .

Micov, Ana, Tomić, Maja, Todorović, Marija B., Vuković, Milja, Pecikoza, Uroš, Jasnić, Nebojša, Đorđević, Jelena D., Stepanović-Petrović, Radica, "Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy" in Progress in Neuro-Psychopharmacology and Biological Psychiatry, 103 (2020),
https://doi.org/10.1016/j.pnpbp.2020.109975 . .

TY  - JOUR
AU  - Đekić, Ljiljana
AU  - Marković, Bojan
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Stepanović-Petrović, Radica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3589
AB  - The study focused on formulation of carmellose sodium hydrogels and nonionic microemulsions with 5% and 10% of levetiracetam and investigation of drug concentration influence on their physicochemical characteristics and in-use stability as well as influence of drug concentration and carrier type on in vitro drug release and in vivo antihyperalgesic/antiedematous activity in a rat model of localized (intraplantar) carrageenan-induced inflammation. Hydrogels were pseudoplastic semisolids with thixotropy and pH 7.37–7.58. Microemulsions were low viscous Newtonian nanodispersions of oil droplets (13.11–15.11 nm) in water, with pH 4.01–4.64. Physical stability of the investigated systems was preserved over the 3-month storage under ambient conditions. Levetiracetam release followed zero order and Korsmeyer-Peppas models (R2 ≥ 0.99) reflecting the combined effects of drug concentration and carrier viscosity. All levetiracetam-loaded formulations produced significant reduction of hyperalgesia and paw swelling induced by carrageenan (p < 0.001). Their efficacy in exerting antihyperalgesic activity was significantly higher than that observed with the reference 5% ibuprofen hydrogel preparation (up to 6 h) (p < 0.001), while antiedematous activity was comparable with the reference product. No erythema and visible blood vessels were observed in a rat ear test. The study demonstrated percutaneous delivery of levetiracetam as useful and safe therapeutic option for localized inflammatory pain with potential to overcome the insufficient efficacy of topically applied nonsteroidal anti-inflammatory drugs in the form of a hydrogel. [Figure not available: see fulltext.]. © 2020, Controlled Release Society.
PB  - Springer
T2  - Drug Delivery and Translational Research
T1  - Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization
DO  - 10.1007/s13346-020-00787-4
ER  - 

@article{
author = "Đekić, Ljiljana and Marković, Bojan and Micov, Ana and Tomić, Maja and Pecikoza, Uroš and Stepanović-Petrović, Radica",
year = "2020",
abstract = "The study focused on formulation of carmellose sodium hydrogels and nonionic microemulsions with 5% and 10% of levetiracetam and investigation of drug concentration influence on their physicochemical characteristics and in-use stability as well as influence of drug concentration and carrier type on in vitro drug release and in vivo antihyperalgesic/antiedematous activity in a rat model of localized (intraplantar) carrageenan-induced inflammation. Hydrogels were pseudoplastic semisolids with thixotropy and pH 7.37–7.58. Microemulsions were low viscous Newtonian nanodispersions of oil droplets (13.11–15.11 nm) in water, with pH 4.01–4.64. Physical stability of the investigated systems was preserved over the 3-month storage under ambient conditions. Levetiracetam release followed zero order and Korsmeyer-Peppas models (R2 ≥ 0.99) reflecting the combined effects of drug concentration and carrier viscosity. All levetiracetam-loaded formulations produced significant reduction of hyperalgesia and paw swelling induced by carrageenan (p < 0.001). Their efficacy in exerting antihyperalgesic activity was significantly higher than that observed with the reference 5% ibuprofen hydrogel preparation (up to 6 h) (p < 0.001), while antiedematous activity was comparable with the reference product. No erythema and visible blood vessels were observed in a rat ear test. The study demonstrated percutaneous delivery of levetiracetam as useful and safe therapeutic option for localized inflammatory pain with potential to overcome the insufficient efficacy of topically applied nonsteroidal anti-inflammatory drugs in the form of a hydrogel. [Figure not available: see fulltext.]. © 2020, Controlled Release Society.",
publisher = "Springer",
journal = "Drug Delivery and Translational Research",
title = "Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization",
doi = "10.1007/s13346-020-00787-4"
}

Đekić, L., Marković, B., Micov, A., Tomić, M., Pecikoza, U.,& Stepanović-Petrović, R.. (2020). Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization. in Drug Delivery and Translational Research
Springer..
https://doi.org/10.1007/s13346-020-00787-4

Đekić L, Marković B, Micov A, Tomić M, Pecikoza U, Stepanović-Petrović R. Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization. in Drug Delivery and Translational Research. 2020;.
doi:10.1007/s13346-020-00787-4 .

Đekić, Ljiljana, Marković, Bojan, Micov, Ana, Tomić, Maja, Pecikoza, Uroš, Stepanović-Petrović, Radica, "Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization" in Drug Delivery and Translational Research (2020),
https://doi.org/10.1007/s13346-020-00787-4 . .

TY  - JOUR
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Micov, Ana
AU  - Vuković, Milja
AU  - Stepanović-Petrović, Radica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3547
AB  - Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified. Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain. Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis. Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively). Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.
PB  - Springer Nature
T2  - Psychopharmacology
T1  - Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception
VL  - 237
IS  - 5
SP  - 1435
EP  - 1446
DO  - 10.1007/s00213-020-05470-7
ER  - 

@article{
author = "Pecikoza, Uroš and Tomić, Maja and Micov, Ana and Vuković, Milja and Stepanović-Petrović, Radica",
year = "2020",
abstract = "Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified. Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain. Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis. Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively). Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.",
publisher = "Springer Nature",
journal = "Psychopharmacology",
title = "Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception",
volume = "237",
number = "5",
pages = "1435-1446",
doi = "10.1007/s00213-020-05470-7"
}

Pecikoza, U., Tomić, M., Micov, A., Vuković, M.,& Stepanović-Petrović, R.. (2020). Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception. in Psychopharmacology
Springer Nature., 237(5), 1435-1446.
https://doi.org/10.1007/s00213-020-05470-7

Pecikoza U, Tomić M, Micov A, Vuković M, Stepanović-Petrović R. Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception. in Psychopharmacology. 2020;237(5):1435-1446.
doi:10.1007/s00213-020-05470-7 .

Pecikoza, Uroš, Tomić, Maja, Micov, Ana, Vuković, Milja, Stepanović-Petrović, Radica, "Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception" in Psychopharmacology, 237, no. 5 (2020):1435-1446,
https://doi.org/10.1007/s00213-020-05470-7 . .

TY  - JOUR
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Micov, Ana
AU  - Vuković, Milja
AU  - Stepanović-Petrović, Radica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3546
AB  - Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified.
Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain.
Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis.
Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively).
Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.
PB  - Springer-Verlag
T2  - Psychopharmacology
T1  - Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception
DO  - 10.1007/s00213-020-05470-7
ER  - 

@article{
author = "Pecikoza, Uroš and Tomić, Maja and Micov, Ana and Vuković, Milja and Stepanović-Petrović, Radica",
year = "2020",
abstract = "Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified.
Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain.
Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis.
Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively).
Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.",
publisher = "Springer-Verlag",
journal = "Psychopharmacology",
title = "Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception",
doi = "10.1007/s00213-020-05470-7"
}

Pecikoza, U., Tomić, M., Micov, A., Vuković, M.,& Stepanović-Petrović, R.. (2020). Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception. in Psychopharmacology
Springer-Verlag..
https://doi.org/10.1007/s00213-020-05470-7

Pecikoza U, Tomić M, Micov A, Vuković M, Stepanović-Petrović R. Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception. in Psychopharmacology. 2020;.
doi:10.1007/s00213-020-05470-7 .

Pecikoza, Uroš, Tomić, Maja, Micov, Ana, Vuković, Milja, Stepanović-Petrović, Radica, "Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception" in Psychopharmacology (2020),
https://doi.org/10.1007/s00213-020-05470-7 . .

TY  - JOUR
AU  - Micov, Ana
AU  - Pecikoza, Uroš
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3599
AB  - Alzheimer’s disease (AD), the most common cause of dementia, is growing health, social and economic issue because of the increasing number of sufferers, limited efficacy of available treatment options, and high total healthcare costs. It is clinically characterized by cognitive and behavioral impairments, both of which need to be treated appropriately to improve patients’ quality  of  life  and  their  caregivers  as  well.  Currently,  available  anti-dementia  medications provide only modest and transient cognitive benefits. Donepezil, rivastigmine and galantamine (cholinesterase inhibitors) are indicated for the symptomatic management of mild to moderately severe  AD,  while  memantine  (NMDA  glutamate  receptors  antagonist)  is  recommended  for moderate-to-severe  AD.  A  special  focus  on  behavioral  symptoms  (e.g.  anxiety,  depression, aggression) management is required as they cause great suffering in patients/caregivers. The use of medications that can impair cognitive function, such as drugs with anticholinergic activity, should  be  avoided  in  patients  with  dementia.  Additionally,  interventions  that  could  delay  or prevent  dementia  onset  in  some  subjects  are  focused  on  minimizing  modifiable  risk  factors (hypertension,  diabetes,  depression)  and  maximizing  protective factors  (physical  activity, healthy diet, leisure, and social activities). The treatment of AD remains a challenge.
AB  - Alzheimer-ova bolest (AB), najčešći oblik demencije, rastući je zdravstveni, socijalni i ekonomski problem zbog sve većeg broja obolelih, nedovoljne efikasnosti postojećih terapijskih mera, kao i velikih ukupnih troškova nege. Klinički se manifestuje smanjenjem kognitivnih funkcija i poremećajima ponašanja, koje treba adekvatno lečiti kako bi se popravio kvalitet života obolelih i njihovih negovatelja. Raspoloživi lekovi za lečenje demencija ostvaruju umereno i prolazno poboljšanje kognitivnih funkcija. Donepezil, rivastigmin i galantamin (inhibitori holinesteraza) su indikovani kao simptomatska terapija blage do umereno teške forme AB, dok se memantin (antagonist glutamatergičkih NMDA receptora) preporučuje za lečenje umerene do teške AB. Poseban aspekt lečenja predstavlja terapija bihejvioralnih simptoma (anksioznost, depresija, agresivnost), koji su veliki problem za pacijente i negovatelje. Trebalo bi izbegavati primenu lekova koji nepovoljno utiču na kogniciju, kao što su lekovi sa antiholinegičkim dejstvom, kod pacijenata sa demencijom. Dodatno, kontrola promenljivih faktora rizika (hipertenzija, dijabetes, depresija) i usvajanje protektivnih faktora (fizička aktivnost, zdrava ishrana, socijalne aktivnosti i aktivnosti u slobodno vreme) možda može da spreči ili odloži pojavu demencije kod izvesnih ljudi. Lečenje AB i dalje je veliki izazov.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Anti-dementia medications –  fighting a losing battle?
T1  - Lekovi u lečenju demencija - unapred izgubljena bitka?
VL  - 70
IS  - 2
SP  - 55
EP  - 68
DO  - 10.5937/arhfarm2002055M
ER  - 

@article{
author = "Micov, Ana and Pecikoza, Uroš",
year = "2020",
abstract = "Alzheimer’s disease (AD), the most common cause of dementia, is growing health, social and economic issue because of the increasing number of sufferers, limited efficacy of available treatment options, and high total healthcare costs. It is clinically characterized by cognitive and behavioral impairments, both of which need to be treated appropriately to improve patients’ quality  of  life  and  their  caregivers  as  well.  Currently,  available  anti-dementia  medications provide only modest and transient cognitive benefits. Donepezil, rivastigmine and galantamine (cholinesterase inhibitors) are indicated for the symptomatic management of mild to moderately severe  AD,  while  memantine  (NMDA  glutamate  receptors  antagonist)  is  recommended  for moderate-to-severe  AD.  A  special  focus  on  behavioral  symptoms  (e.g.  anxiety,  depression, aggression) management is required as they cause great suffering in patients/caregivers. The use of medications that can impair cognitive function, such as drugs with anticholinergic activity, should  be  avoided  in  patients  with  dementia.  Additionally,  interventions  that  could  delay  or prevent  dementia  onset  in  some  subjects  are  focused  on  minimizing  modifiable  risk  factors (hypertension,  diabetes,  depression)  and  maximizing  protective factors  (physical  activity, healthy diet, leisure, and social activities). The treatment of AD remains a challenge., Alzheimer-ova bolest (AB), najčešći oblik demencije, rastući je zdravstveni, socijalni i ekonomski problem zbog sve većeg broja obolelih, nedovoljne efikasnosti postojećih terapijskih mera, kao i velikih ukupnih troškova nege. Klinički se manifestuje smanjenjem kognitivnih funkcija i poremećajima ponašanja, koje treba adekvatno lečiti kako bi se popravio kvalitet života obolelih i njihovih negovatelja. Raspoloživi lekovi za lečenje demencija ostvaruju umereno i prolazno poboljšanje kognitivnih funkcija. Donepezil, rivastigmin i galantamin (inhibitori holinesteraza) su indikovani kao simptomatska terapija blage do umereno teške forme AB, dok se memantin (antagonist glutamatergičkih NMDA receptora) preporučuje za lečenje umerene do teške AB. Poseban aspekt lečenja predstavlja terapija bihejvioralnih simptoma (anksioznost, depresija, agresivnost), koji su veliki problem za pacijente i negovatelje. Trebalo bi izbegavati primenu lekova koji nepovoljno utiču na kogniciju, kao što su lekovi sa antiholinegičkim dejstvom, kod pacijenata sa demencijom. Dodatno, kontrola promenljivih faktora rizika (hipertenzija, dijabetes, depresija) i usvajanje protektivnih faktora (fizička aktivnost, zdrava ishrana, socijalne aktivnosti i aktivnosti u slobodno vreme) možda može da spreči ili odloži pojavu demencije kod izvesnih ljudi. Lečenje AB i dalje je veliki izazov.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije, Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Anti-dementia medications –  fighting a losing battle?, Lekovi u lečenju demencija - unapred izgubljena bitka?",
volume = "70",
number = "2",
pages = "55-68",
doi = "10.5937/arhfarm2002055M"
}

Micov, A.,& Pecikoza, U.. (2020). Anti-dementia medications –  fighting a losing battle?. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 70(2), 55-68.
https://doi.org/10.5937/arhfarm2002055M

Micov A, Pecikoza U. Anti-dementia medications –  fighting a losing battle?. in Arhiv za farmaciju. 2020;70(2):55-68.
doi:10.5937/arhfarm2002055M .

Micov, Ana, Pecikoza, Uroš, "Anti-dementia medications –  fighting a losing battle?" in Arhiv za farmaciju, 70, no. 2 (2020):55-68,
https://doi.org/10.5937/arhfarm2002055M . .

TY  - CONF
AU  - Milutinović, Violeta
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
AU  - Niketić, Marjan
AU  - Ušjak, Ljuboš
AU  - Petrović, Silvana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5281
AB  - Rod Hieracium s. str. (Asteraceae) je autohton na teritoriji Evroazije, severne Afrike i Severne Amerike, sa velikim brojem taksona rasprostranjenih u Evropi. ...
AB  - Genus Hieracium s. str. (Asteraceae) is autochthonous in Eurasia, North Africa and North America, with the vast majority of taxa being distributed in Europe. ...
PB  - Srpsko farmakološko društvo (SFD)
C3  - 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova
T1  - Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium
T1  - Investigation of antihyperalgesic and antiedematous activities of the flowering aerial parts extracts of three Hieracium species
SP  - 176
EP  - 177
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5281
ER  - 

@conference{
author = "Milutinović, Violeta and Pecikoza, Uroš and Tomić, Maja and Stepanović-Petrović, Radica and Niketić, Marjan and Ušjak, Ljuboš and Petrović, Silvana",
year = "2019",
abstract = "Rod Hieracium s. str. (Asteraceae) je autohton na teritoriji Evroazije, severne Afrike i Severne Amerike, sa velikim brojem taksona rasprostranjenih u Evropi. ..., Genus Hieracium s. str. (Asteraceae) is autochthonous in Eurasia, North Africa and North America, with the vast majority of taxa being distributed in Europe. ...",
publisher = "Srpsko farmakološko društvo (SFD)",
journal = "14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova",
title = "Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium, Investigation of antihyperalgesic and antiedematous activities of the flowering aerial parts extracts of three Hieracium species",
pages = "176-177",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5281"
}

Milutinović, V., Pecikoza, U., Tomić, M., Stepanović-Petrović, R., Niketić, M., Ušjak, L.,& Petrović, S.. (2019). Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium. in 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova
Srpsko farmakološko društvo (SFD)., 176-177.
https://hdl.handle.net/21.15107/rcub_farfar_5281

Milutinović V, Pecikoza U, Tomić M, Stepanović-Petrović R, Niketić M, Ušjak L, Petrović S. Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium. in 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova. 2019;:176-177.
https://hdl.handle.net/21.15107/rcub_farfar_5281 .

Milutinović, Violeta, Pecikoza, Uroš, Tomić, Maja, Stepanović-Petrović, Radica, Niketić, Marjan, Ušjak, Ljuboš, Petrović, Silvana, "Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium" in 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova (2019):176-177,
https://hdl.handle.net/21.15107/rcub_farfar_5281 .

TY  - JOUR
AU  - Dinić, Miroslav
AU  - Pecikoza, Uroš
AU  - Đokić, Jelena
AU  - Stepanović-Petrović, Radica
AU  - Milenković, Marina
AU  - Stevanović, Magdalena
AU  - Filipović, Nenad
AU  - Begović, Jelena
AU  - Golić, Nataša
AU  - Lukić, Jovanka
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3152
AB  - The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS) produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11) to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR) and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia) and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1 beta and iNOS mRNAs in rat's paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1 beta, TNF-alpha and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Pharmacology
T1  - Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats
VL  - 9
DO  - 10.3389/fphar.2018.00001
ER  - 

@article{
author = "Dinić, Miroslav and Pecikoza, Uroš and Đokić, Jelena and Stepanović-Petrović, Radica and Milenković, Marina and Stevanović, Magdalena and Filipović, Nenad and Begović, Jelena and Golić, Nataša and Lukić, Jovanka",
year = "2018",
abstract = "The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS) produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11) to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR) and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia) and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1 beta and iNOS mRNAs in rat's paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1 beta, TNF-alpha and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Pharmacology",
title = "Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats",
volume = "9",
doi = "10.3389/fphar.2018.00001"
}

Dinić, M., Pecikoza, U., Đokić, J., Stepanović-Petrović, R., Milenković, M., Stevanović, M., Filipović, N., Begović, J., Golić, N.,& Lukić, J.. (2018). Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats. in Frontiers in Pharmacology
Frontiers Media Sa, Lausanne., 9.
https://doi.org/10.3389/fphar.2018.00001

Dinić M, Pecikoza U, Đokić J, Stepanović-Petrović R, Milenković M, Stevanović M, Filipović N, Begović J, Golić N, Lukić J. Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats. in Frontiers in Pharmacology. 2018;9.
doi:10.3389/fphar.2018.00001 .

Dinić, Miroslav, Pecikoza, Uroš, Đokić, Jelena, Stepanović-Petrović, Radica, Milenković, Marina, Stevanović, Magdalena, Filipović, Nenad, Begović, Jelena, Golić, Nataša, Lukić, Jovanka, "Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats" in Frontiers in Pharmacology, 9 (2018),
https://doi.org/10.3389/fphar.2018.00001 . .

TY  - JOUR
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Vučković, Sonja M.
AU  - Stepanović-Petrović, Radica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3122
AB  - Inflammatory pain is the most common type of pain that is treated clinically. The use of currently available treatments (classic analgesics - NSAID5, paracetamol and opioids) is limited by insufficient efficacy and/or side effects/ tolerance development. Antiepileptic drugs (AEDs) are widely used in neuropathic pain treatment, but there is substantial preclinical evidence on their efficacy against inflammatory pain, too. In this review we focus on gabapentinoids (gabapentin and pregabalin) and dibenzazepine AEDs (carbamazepine, oxcarbazepine, and recently introduced eslicarbazepine acetate) and their potential for relieving inflammatory pain. In models of somatic, visceral and trigeminal inflammatory pain, that have a translational value for inflammatory conditions in locomotor system, viscera and head/face, AEDs have demonstrated analgesic activity. This activity was mostly consistent, dependent on the dose and largely independent on the site of inflammation and method of its induction, nociceptive stimuli, species, specific drug used, its route of administration and dosing schedule. AEDs exerted comparable efficacy with classic analgesics. Effective doses of AEDs are lower than toxic doses in animals and, when expressed as equivalent human doses, they are largely overlapping with AEDs doses already used in humans for treating epilepsy/neuropathic pain. The main mechanism of antinociceptive/antihyperalgesic action of gabapentinoids in inflammatory pain models seems to be alpha 2 delta-dependent suppression of voltage -gated calcium channels in primary sensory neurons that leads to reduced release of neurotransmitters in the spinal/medullar dorsal horn. The suppression of NMDA receptors via co-agonist binding site primarily at spinal sites, activation of various types of K+ channels at spinal and peripheral sites, and activation of noradrenergic and serotonergic descending pain modulatory pathways may also contribute. Inhibition of voltage -gated sodium channels along the pain pathway is probably the main mechanism of antinociceptive/antihyperalgesic effects of dibenzazepines. The recruitment of peripheral adrenergic and purinergic mechanisms and central GABAergic mechanisms may also contribute. When co-administered with classic/other alternative analgesics, AEDs exerted synergistic/additive interactions. Reviewed data could serve as a basis for clinical studies on the efficacy/safety of AEDs as analgesics/adjuvants in patients with inflammatory pain, and contribute to the improvement of the treatment of various inflammatory pain states.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Pharmacology & Therapeutics
T1  - Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence
VL  - 192
SP  - 42
EP  - 64
DO  - 10.1016/j.pharmthera.2018.06.002
ER  - 

@article{
author = "Tomić, Maja and Pecikoza, Uroš and Micov, Ana and Vučković, Sonja M. and Stepanović-Petrović, Radica",
year = "2018",
abstract = "Inflammatory pain is the most common type of pain that is treated clinically. The use of currently available treatments (classic analgesics - NSAID5, paracetamol and opioids) is limited by insufficient efficacy and/or side effects/ tolerance development. Antiepileptic drugs (AEDs) are widely used in neuropathic pain treatment, but there is substantial preclinical evidence on their efficacy against inflammatory pain, too. In this review we focus on gabapentinoids (gabapentin and pregabalin) and dibenzazepine AEDs (carbamazepine, oxcarbazepine, and recently introduced eslicarbazepine acetate) and their potential for relieving inflammatory pain. In models of somatic, visceral and trigeminal inflammatory pain, that have a translational value for inflammatory conditions in locomotor system, viscera and head/face, AEDs have demonstrated analgesic activity. This activity was mostly consistent, dependent on the dose and largely independent on the site of inflammation and method of its induction, nociceptive stimuli, species, specific drug used, its route of administration and dosing schedule. AEDs exerted comparable efficacy with classic analgesics. Effective doses of AEDs are lower than toxic doses in animals and, when expressed as equivalent human doses, they are largely overlapping with AEDs doses already used in humans for treating epilepsy/neuropathic pain. The main mechanism of antinociceptive/antihyperalgesic action of gabapentinoids in inflammatory pain models seems to be alpha 2 delta-dependent suppression of voltage -gated calcium channels in primary sensory neurons that leads to reduced release of neurotransmitters in the spinal/medullar dorsal horn. The suppression of NMDA receptors via co-agonist binding site primarily at spinal sites, activation of various types of K+ channels at spinal and peripheral sites, and activation of noradrenergic and serotonergic descending pain modulatory pathways may also contribute. Inhibition of voltage -gated sodium channels along the pain pathway is probably the main mechanism of antinociceptive/antihyperalgesic effects of dibenzazepines. The recruitment of peripheral adrenergic and purinergic mechanisms and central GABAergic mechanisms may also contribute. When co-administered with classic/other alternative analgesics, AEDs exerted synergistic/additive interactions. Reviewed data could serve as a basis for clinical studies on the efficacy/safety of AEDs as analgesics/adjuvants in patients with inflammatory pain, and contribute to the improvement of the treatment of various inflammatory pain states.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Pharmacology & Therapeutics",
title = "Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence",
volume = "192",
pages = "42-64",
doi = "10.1016/j.pharmthera.2018.06.002"
}

Tomić, M., Pecikoza, U., Micov, A., Vučković, S. M.,& Stepanović-Petrović, R.. (2018). Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence. in Pharmacology & Therapeutics
Pergamon-Elsevier Science Ltd, Oxford., 192, 42-64.
https://doi.org/10.1016/j.pharmthera.2018.06.002

Tomić M, Pecikoza U, Micov A, Vučković SM, Stepanović-Petrović R. Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence. in Pharmacology & Therapeutics. 2018;192:42-64.
doi:10.1016/j.pharmthera.2018.06.002 .

Tomić, Maja, Pecikoza, Uroš, Micov, Ana, Vučković, Sonja M., Stepanović-Petrović, Radica, "Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence" in Pharmacology & Therapeutics, 192 (2018):42-64,
https://doi.org/10.1016/j.pharmthera.2018.06.002 . .

TY  - JOUR
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3061
AB  - Aims: Eslicarbazepine acetate (ESL) is a novel dibenzazepine antiepileptic, that has demonstrated efficacy against trigeminal pain, both in preclinical and clinical studies. However, ESL's mechanism of antinociceptive action remains uncertain. Here, we aimed to examine the contribution of adrenergic/cholinergic/opioid receptors to the antinociceptive effects of ESL in a trigeminal pain model, as these neurotransmitter systems are known to have an important role in the modulation of trigeminal nociception. Main methods: ESL's effects in the orofacial formalin test were examined following peroral and local peripheral administration (subcutaneous, into the perinasal region). The involvement of adrenergic/cholinergic/opioid receptors was evaluated by intraperitoneally pretreating mice with an appropriate antagonist immediately after peroral application of ESL. We used antagonists of alpha(1)-adrenergic (prazosin), alpha(2)-adrenergic (yohimbine), beta(3)-adrenergic (non-selective, propranolol and beta(1)-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral alpha(2)-adrenergic, beta(1)-adrenergic, muscarinic and opioid receptors was evaluated by co-injecting ESL with an antagonist into the perinasal area. Key findings: ESL dose-dependently reduced formalin-induced nociceptive behavior after systemic and local peripheral application. Systemic administration of yohimbine, propranolol, metoprolol, atropine and naloxone inhibited ESL's antinociceptive effects in a dose-related manner. Prazosin and mecamylamine did not produce inhibitory effects. Local application of yohimbine, atropine and naloxone into the perinasal area also produced a dose-related inhibition of ESL's efficacy, whereas metoprolol failed to inhibit the local antinociceptive effects of ESL. Significance: This study suggests that ESL's efficacy against trigeminal nociception is mediated by peripheral (and possibly central) alpha(2)-adrenergic, muscarinic and opioid receptors, as well as central beta(1)-adrenergic receptors.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Life Sciences
T1  - Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors
VL  - 214
SP  - 167
EP  - 175
DO  - 10.1016/j.lfs.2018.10.059
ER  - 

@article{
author = "Pecikoza, Uroš and Micov, Ana and Tomić, Maja and Stepanović-Petrović, Radica",
year = "2018",
abstract = "Aims: Eslicarbazepine acetate (ESL) is a novel dibenzazepine antiepileptic, that has demonstrated efficacy against trigeminal pain, both in preclinical and clinical studies. However, ESL's mechanism of antinociceptive action remains uncertain. Here, we aimed to examine the contribution of adrenergic/cholinergic/opioid receptors to the antinociceptive effects of ESL in a trigeminal pain model, as these neurotransmitter systems are known to have an important role in the modulation of trigeminal nociception. Main methods: ESL's effects in the orofacial formalin test were examined following peroral and local peripheral administration (subcutaneous, into the perinasal region). The involvement of adrenergic/cholinergic/opioid receptors was evaluated by intraperitoneally pretreating mice with an appropriate antagonist immediately after peroral application of ESL. We used antagonists of alpha(1)-adrenergic (prazosin), alpha(2)-adrenergic (yohimbine), beta(3)-adrenergic (non-selective, propranolol and beta(1)-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral alpha(2)-adrenergic, beta(1)-adrenergic, muscarinic and opioid receptors was evaluated by co-injecting ESL with an antagonist into the perinasal area. Key findings: ESL dose-dependently reduced formalin-induced nociceptive behavior after systemic and local peripheral application. Systemic administration of yohimbine, propranolol, metoprolol, atropine and naloxone inhibited ESL's antinociceptive effects in a dose-related manner. Prazosin and mecamylamine did not produce inhibitory effects. Local application of yohimbine, atropine and naloxone into the perinasal area also produced a dose-related inhibition of ESL's efficacy, whereas metoprolol failed to inhibit the local antinociceptive effects of ESL. Significance: This study suggests that ESL's efficacy against trigeminal nociception is mediated by peripheral (and possibly central) alpha(2)-adrenergic, muscarinic and opioid receptors, as well as central beta(1)-adrenergic receptors.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Life Sciences",
title = "Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors",
volume = "214",
pages = "167-175",
doi = "10.1016/j.lfs.2018.10.059"
}

Pecikoza, U., Micov, A., Tomić, M.,& Stepanović-Petrović, R.. (2018). Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors. in Life Sciences
Pergamon-Elsevier Science Ltd, Oxford., 214, 167-175.
https://doi.org/10.1016/j.lfs.2018.10.059

Pecikoza U, Micov A, Tomić M, Stepanović-Petrović R. Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors. in Life Sciences. 2018;214:167-175.
doi:10.1016/j.lfs.2018.10.059 .

Pecikoza, Uroš, Micov, Ana, Tomić, Maja, Stepanović-Petrović, Radica, "Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors" in Life Sciences, 214 (2018):167-175,
https://doi.org/10.1016/j.lfs.2018.10.059 . .

TY  - JOUR
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Micov, Ana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3108
AB  - Pain is a symptom of most diseases that can significantly impair the patient's quality of life. In many diseases it is impossible to eliminate the cause of pain therefore the real goal of treatment is the removal of pain as a symptom, by application of analgesics. Contemporary pharmacotherapy employs conventional (opioid and non-opioid analgesics - NSAIDs and paracetamol) and adjuvant analgesics (antiepileptics, antidepressants and others). Analgesic effect of non-opioid analgesics is mainly the consequence of prostaglandin synthesis inhibition. They are effective for pain of mild/moderate intensity. In acute pain there is no difference in efficiency between NSAIDs and paracetamol, so the choice of the drug is individual. In chronic pain, when inflammation is present, NSAIDs are more effective than paracetamol. Long-term use of high doses of NSAIDs is often accompanied by side effects. In order to reduce their frequency, a careful assessment of risk for each patient should be made, a drug with a low risk of certain side effects should be chosen, the dose and duration of treatment should be limited and the possibility of topical application should be considered. The need for long-term use of NSAIDs should be reviewed periodically.
AB  - Bol je simptom većine oboljenja koji može značajno narušiti kvalitet života pacijenta. Kod mnogih oboljenja nemoguće je otkloniti uzrok bola, stoga je realni cilj lečenja uklanjanje bola kao simptoma, primenom analgetika. Savremena farmakoterapija raspolaže klasičnim (opioidni i ne-opiodini analgetici: NSAIL i paracetamol) i adjuvantnim analgeticima (antiepileptici, antidepresivi i drugi). Analgetičko dejstvo ne-opioidnih analgetika uglavnom je posledica inhibicije sinteze prostaglandina. Efikasni su kod bola blagog/umerenog intenziteta. Kod akutnog bola nema razlike u efikasnosti između NSAIL i paracetamola pa je izbor leka individualan. NSAIL su efikasniji kod hroničnih bolnih stanja u kojima je prisutna inflamacija, ali njihovu dugotrajnu primenu često prate neželjena dejstva. Kako bi se smanjila učestalost neželjenih efekata NSAIL, treba izvršiti pažljivu procenu rizika za svakog pacijenta, odabrati lek sa niskim rizikom za određeno neželjeno dejstvo, ograničiti dozu i trajanje tretmana i razmotriti mogućnost topikalne primene. Potrebu za dugotrajnom primenom NSAIL treba povremeno preispitivati.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Non-opioid analgesics in contemporary treatment of pain
T1  - Neopioidni analgetici u savremenom lečenju bola
VL  - 68
IS  - 6
SP  - 1021
EP  - 1031
DO  - 10.5937/ArhFarm1806021T
ER  - 

@article{
author = "Tomić, Maja and Pecikoza, Uroš and Micov, Ana",
year = "2018",
abstract = "Pain is a symptom of most diseases that can significantly impair the patient's quality of life. In many diseases it is impossible to eliminate the cause of pain therefore the real goal of treatment is the removal of pain as a symptom, by application of analgesics. Contemporary pharmacotherapy employs conventional (opioid and non-opioid analgesics - NSAIDs and paracetamol) and adjuvant analgesics (antiepileptics, antidepressants and others). Analgesic effect of non-opioid analgesics is mainly the consequence of prostaglandin synthesis inhibition. They are effective for pain of mild/moderate intensity. In acute pain there is no difference in efficiency between NSAIDs and paracetamol, so the choice of the drug is individual. In chronic pain, when inflammation is present, NSAIDs are more effective than paracetamol. Long-term use of high doses of NSAIDs is often accompanied by side effects. In order to reduce their frequency, a careful assessment of risk for each patient should be made, a drug with a low risk of certain side effects should be chosen, the dose and duration of treatment should be limited and the possibility of topical application should be considered. The need for long-term use of NSAIDs should be reviewed periodically., Bol je simptom većine oboljenja koji može značajno narušiti kvalitet života pacijenta. Kod mnogih oboljenja nemoguće je otkloniti uzrok bola, stoga je realni cilj lečenja uklanjanje bola kao simptoma, primenom analgetika. Savremena farmakoterapija raspolaže klasičnim (opioidni i ne-opiodini analgetici: NSAIL i paracetamol) i adjuvantnim analgeticima (antiepileptici, antidepresivi i drugi). Analgetičko dejstvo ne-opioidnih analgetika uglavnom je posledica inhibicije sinteze prostaglandina. Efikasni su kod bola blagog/umerenog intenziteta. Kod akutnog bola nema razlike u efikasnosti između NSAIL i paracetamola pa je izbor leka individualan. NSAIL su efikasniji kod hroničnih bolnih stanja u kojima je prisutna inflamacija, ali njihovu dugotrajnu primenu često prate neželjena dejstva. Kako bi se smanjila učestalost neželjenih efekata NSAIL, treba izvršiti pažljivu procenu rizika za svakog pacijenta, odabrati lek sa niskim rizikom za određeno neželjeno dejstvo, ograničiti dozu i trajanje tretmana i razmotriti mogućnost topikalne primene. Potrebu za dugotrajnom primenom NSAIL treba povremeno preispitivati.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Non-opioid analgesics in contemporary treatment of pain, Neopioidni analgetici u savremenom lečenju bola",
volume = "68",
number = "6",
pages = "1021-1031",
doi = "10.5937/ArhFarm1806021T"
}

Tomić, M., Pecikoza, U.,& Micov, A.. (2018). Non-opioid analgesics in contemporary treatment of pain. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 68(6), 1021-1031.
https://doi.org/10.5937/ArhFarm1806021T

Tomić M, Pecikoza U, Micov A. Non-opioid analgesics in contemporary treatment of pain. in Arhiv za farmaciju. 2018;68(6):1021-1031.
doi:10.5937/ArhFarm1806021T .

Tomić, Maja, Pecikoza, Uroš, Micov, Ana, "Non-opioid analgesics in contemporary treatment of pain" in Arhiv za farmaciju, 68, no. 6 (2018):1021-1031,
https://doi.org/10.5937/ArhFarm1806021T . .

TY  - JOUR
AU  - Stepanović-Petrović, Radica
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3023
AB  - Rationale We have reported that levetiracetam, a novel anticonvulsant with analgesic properties, synergizes with ibuprofen/aspirin/paracetamol in a model of diabetic painful neuropathy (DPN). Most guidelines recommend gabapentin, pregabalin, and duloxetine as first-or second-line agents for DPN. Objective We examined the effects of combination treatment of first-/second-line analgesics with levetiracetam in a model of DPN. Additionally, the levetiracetam's combinations with antioxidants, low dose of aspirin, coenzyme Q10, or alpha-lipoic acid were evaluated. Methods Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin. The antinociceptive effects of orally administered levetiracetam, gabapentin, pregabalin, duloxetine (acute treatment) and aspirin, coenzyme Q10, and alpha-lipoic acid (preventive 7-day treatment), as well as combinations of levetiracetam with individual drugs were examined in the tail-flick test. In combination experiments, the drugs were coadministered in fixed-dose fractions of single-drug ED50; the type of interaction was determined by isobolographic analysis. Results About 60-, 32-, 30-, 26-, 18-, and 6-fold reductions of doses of both drugs in levetiracetam combinations with pregabalin, gabapentin, coenzyme Q10, aspirin, duloxetine, and alpha-lipoic acid, respectively, were detected. Conclusions Combinations of levetiracetam with gabapentin/pregabalin/duloxetine that target different mechanisms/sites of action involved in DPN, as well as combinations of levetiracetam and low-dose aspirin/coenzyme Q10/alpha-lipoic acid that target underlying causes of DPN, produce marked synergistic interactions in reducing nociception in diabetic mice. This suggests that these combination treatments might be of great benefit for diabetic patients and should be explored further in clinical trials.
PB  - Springer, New York
T2  - QSAR & Combinatorial Science
T1  - Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model
VL  - 234
IS  - 11
SP  - 1781
EP  - 1794
DO  - 10.1007/s00213-017-4583-z
ER  - 

@article{
author = "Stepanović-Petrović, Radica and Micov, Ana and Tomić, Maja and Pecikoza, Uroš",
year = "2017",
abstract = "Rationale We have reported that levetiracetam, a novel anticonvulsant with analgesic properties, synergizes with ibuprofen/aspirin/paracetamol in a model of diabetic painful neuropathy (DPN). Most guidelines recommend gabapentin, pregabalin, and duloxetine as first-or second-line agents for DPN. Objective We examined the effects of combination treatment of first-/second-line analgesics with levetiracetam in a model of DPN. Additionally, the levetiracetam's combinations with antioxidants, low dose of aspirin, coenzyme Q10, or alpha-lipoic acid were evaluated. Methods Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin. The antinociceptive effects of orally administered levetiracetam, gabapentin, pregabalin, duloxetine (acute treatment) and aspirin, coenzyme Q10, and alpha-lipoic acid (preventive 7-day treatment), as well as combinations of levetiracetam with individual drugs were examined in the tail-flick test. In combination experiments, the drugs were coadministered in fixed-dose fractions of single-drug ED50; the type of interaction was determined by isobolographic analysis. Results About 60-, 32-, 30-, 26-, 18-, and 6-fold reductions of doses of both drugs in levetiracetam combinations with pregabalin, gabapentin, coenzyme Q10, aspirin, duloxetine, and alpha-lipoic acid, respectively, were detected. Conclusions Combinations of levetiracetam with gabapentin/pregabalin/duloxetine that target different mechanisms/sites of action involved in DPN, as well as combinations of levetiracetam and low-dose aspirin/coenzyme Q10/alpha-lipoic acid that target underlying causes of DPN, produce marked synergistic interactions in reducing nociception in diabetic mice. This suggests that these combination treatments might be of great benefit for diabetic patients and should be explored further in clinical trials.",
publisher = "Springer, New York",
journal = "QSAR & Combinatorial Science",
title = "Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model",
volume = "234",
number = "11",
pages = "1781-1794",
doi = "10.1007/s00213-017-4583-z"
}

Stepanović-Petrović, R., Micov, A., Tomić, M.,& Pecikoza, U.. (2017). Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model. in QSAR & Combinatorial Science
Springer, New York., 234(11), 1781-1794.
https://doi.org/10.1007/s00213-017-4583-z

Stepanović-Petrović R, Micov A, Tomić M, Pecikoza U. Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model. in QSAR & Combinatorial Science. 2017;234(11):1781-1794.
doi:10.1007/s00213-017-4583-z .

Stepanović-Petrović, Radica, Micov, Ana, Tomić, Maja, Pecikoza, Uroš, "Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model" in QSAR & Combinatorial Science, 234, no. 11 (2017):1781-1794,
https://doi.org/10.1007/s00213-017-4583-z . .

TY  - CHAP
AU  - Tomić, Maja
AU  - Micov, Ana
AU  - Pecikoza, Uroš
AU  - Stepanović-Petrović, Radica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2967
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world. They act via inhibition of cyclooxygenase (COX) isoenzymes. The combined analgesic, anti-inflammatory, and antipyretic effects make NSAIDs especially useful for symptomatic relief of painful inflammatory conditions and fever. They are used for treating musculoskeletal disorders (chronic, like osteoarthritis and rheumatoid arthritis, and acute, like acute gout and injuries), headaches, dental and postoperative pain, and dysmenorrhea, and aspirin also for prevention of cardiovascular events. NSAIDs may cause serious gastrointestinal, cardiovascular, and renal adverse effects, which may be prevented by performing risk assessments for each patient, choosing a NSAID with low risk for the particular side effect, and limiting its dosage and treatment duration. Gastroprotective agents are recommended for gastroduodenal ulcers prevention. Topical NSAIDs application offers a possibility for minimization of all systemic NSAIDs side effects, as well as drug-drug interactions. Evidence supports topical NSAIDs use in hands and knees osteoarthritis, and probably also in acute musculoskeletal pain. They can cause local skin irritation. Modified-release oral preparations improve patient compliance, and are especially important for short-acting NSAIDs. Topical modified-release preparations could improve efficacy and tolerability of NSAIDs topical treatment, and patient compliance.
PB  - Elsevier Inc.
T2  - Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a
T1  - Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations
SP  - 1
EP  - 29
DO  - 10.1016/B978-0-12-804017-1.00001-7
ER  - 

@inbook{
author = "Tomić, Maja and Micov, Ana and Pecikoza, Uroš and Stepanović-Petrović, Radica",
year = "2017",
abstract = "Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world. They act via inhibition of cyclooxygenase (COX) isoenzymes. The combined analgesic, anti-inflammatory, and antipyretic effects make NSAIDs especially useful for symptomatic relief of painful inflammatory conditions and fever. They are used for treating musculoskeletal disorders (chronic, like osteoarthritis and rheumatoid arthritis, and acute, like acute gout and injuries), headaches, dental and postoperative pain, and dysmenorrhea, and aspirin also for prevention of cardiovascular events. NSAIDs may cause serious gastrointestinal, cardiovascular, and renal adverse effects, which may be prevented by performing risk assessments for each patient, choosing a NSAID with low risk for the particular side effect, and limiting its dosage and treatment duration. Gastroprotective agents are recommended for gastroduodenal ulcers prevention. Topical NSAIDs application offers a possibility for minimization of all systemic NSAIDs side effects, as well as drug-drug interactions. Evidence supports topical NSAIDs use in hands and knees osteoarthritis, and probably also in acute musculoskeletal pain. They can cause local skin irritation. Modified-release oral preparations improve patient compliance, and are especially important for short-acting NSAIDs. Topical modified-release preparations could improve efficacy and tolerability of NSAIDs topical treatment, and patient compliance.",
publisher = "Elsevier Inc.",
journal = "Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a",
booktitle = "Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations",
pages = "1-29",
doi = "10.1016/B978-0-12-804017-1.00001-7"
}

Tomić, M., Micov, A., Pecikoza, U.,& Stepanović-Petrović, R.. (2017). Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations. in Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a
Elsevier Inc.., 1-29.
https://doi.org/10.1016/B978-0-12-804017-1.00001-7

Tomić M, Micov A, Pecikoza U, Stepanović-Petrović R. Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations. in Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a. 2017;:1-29.
doi:10.1016/B978-0-12-804017-1.00001-7 .

Tomić, Maja, Micov, Ana, Pecikoza, Uroš, Stepanović-Petrović, Radica, "Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations" in Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a (2017):1-29,
https://doi.org/10.1016/B978-0-12-804017-1.00001-7 . .