TY  - JOUR
AU  - Joksimović, Sonja
AU  - Joksimović, Srđan
AU  - Manzella, Francesca
AU  - Asnake, Betelehem
AU  - Orestes, Peihan
AU  - Raol, Yogendra
AU  - Krishnan, Kathiresan
AU  - Covey, Douglas
AU  - Jevtović-Todorović, Vesna
AU  - Todorović, Slobodan
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3610
AB  - Background and Purpose: Neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) is a novel hypnotic and voltage-dependent blocker of T-type calcium channels. Here, we examine its potential analgesic effects and adjuvant anaesthetic properties using a post-surgical pain model in rodents. Experimental Approach: Analgesic properties of 3β-OH were investigated in thermal and mechanical nociceptive tests in sham or surgically incised rats and mice, with drug injected either systemically (intraperitoneal) or locally via intrathecal or intraplantar routes. Hypnotic properties of 3β-OH and its use as an adjuvant anaesthetic in combination with isoflurane were investigated using behavioural experiments and in vivo EEG recordings in adolescent rats. Key Results: A combination of 1% isoflurane with 3β-OH (60 mg·kg−1, i.p.) induced suppression of cortical EEG and stronger thermal and mechanical anti-hyperalgesia during 3 days post-surgery, when compared to isoflurane alone and isoflurane with morphine. 3β-OH exerted prominent enantioselective thermal and mechanical antinociception in healthy rats and reduced T-channel-dependent excitability of primary sensory neurons. Intrathecal injection of 3β-OH alleviated mechanical hyperalgesia, while repeated intraplantar application alleviated both thermal and mechanical hyperalgesia in the rats after incision. Using mouse genetics, we found that CaV3.2 T-calcium channels are important for anti-hyperalgesic effect of 3β-OH and are contributing to its hypnotic effect. Conclusion and Implications: Our study identifies 3β-OH as a novel analgesic for surgical procedures. 3β-OH can be used to reduce T-channel-dependent excitability of peripheral sensory neurons as an adjuvant for induction and maintenance of general anaesthesia while improving analgesia and lowering the amount of volatile anaesthetic needed for surgery.
PB  - John Wiley and Sons Inc.
T2  - British Journal of Pharmacology
T1  - Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain
VL  - 177
IS  - 8
SP  - 1735
EP  - 1753
DO  - 10.1111/bph.14930
ER  - 

@article{
author = "Joksimović, Sonja and Joksimović, Srđan and Manzella, Francesca and Asnake, Betelehem and Orestes, Peihan and Raol, Yogendra and Krishnan, Kathiresan and Covey, Douglas and Jevtović-Todorović, Vesna and Todorović, Slobodan",
year = "2020",
abstract = "Background and Purpose: Neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) is a novel hypnotic and voltage-dependent blocker of T-type calcium channels. Here, we examine its potential analgesic effects and adjuvant anaesthetic properties using a post-surgical pain model in rodents. Experimental Approach: Analgesic properties of 3β-OH were investigated in thermal and mechanical nociceptive tests in sham or surgically incised rats and mice, with drug injected either systemically (intraperitoneal) or locally via intrathecal or intraplantar routes. Hypnotic properties of 3β-OH and its use as an adjuvant anaesthetic in combination with isoflurane were investigated using behavioural experiments and in vivo EEG recordings in adolescent rats. Key Results: A combination of 1% isoflurane with 3β-OH (60 mg·kg−1, i.p.) induced suppression of cortical EEG and stronger thermal and mechanical anti-hyperalgesia during 3 days post-surgery, when compared to isoflurane alone and isoflurane with morphine. 3β-OH exerted prominent enantioselective thermal and mechanical antinociception in healthy rats and reduced T-channel-dependent excitability of primary sensory neurons. Intrathecal injection of 3β-OH alleviated mechanical hyperalgesia, while repeated intraplantar application alleviated both thermal and mechanical hyperalgesia in the rats after incision. Using mouse genetics, we found that CaV3.2 T-calcium channels are important for anti-hyperalgesic effect of 3β-OH and are contributing to its hypnotic effect. Conclusion and Implications: Our study identifies 3β-OH as a novel analgesic for surgical procedures. 3β-OH can be used to reduce T-channel-dependent excitability of peripheral sensory neurons as an adjuvant for induction and maintenance of general anaesthesia while improving analgesia and lowering the amount of volatile anaesthetic needed for surgery.",
publisher = "John Wiley and Sons Inc.",
journal = "British Journal of Pharmacology",
title = "Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain",
volume = "177",
number = "8",
pages = "1735-1753",
doi = "10.1111/bph.14930"
}

Joksimović, S., Joksimović, S., Manzella, F., Asnake, B., Orestes, P., Raol, Y., Krishnan, K., Covey, D., Jevtović-Todorović, V.,& Todorović, S.. (2020). Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain. in British Journal of Pharmacology
John Wiley and Sons Inc.., 177(8), 1735-1753.
https://doi.org/10.1111/bph.14930

Joksimović S, Joksimović S, Manzella F, Asnake B, Orestes P, Raol Y, Krishnan K, Covey D, Jevtović-Todorović V, Todorović S. Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain. in British Journal of Pharmacology. 2020;177(8):1735-1753.
doi:10.1111/bph.14930 .

Joksimović, Sonja, Joksimović, Srđan, Manzella, Francesca, Asnake, Betelehem, Orestes, Peihan, Raol, Yogendra, Krishnan, Kathiresan, Covey, Douglas, Jevtović-Todorović, Vesna, Todorović, Slobodan, "Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain" in British Journal of Pharmacology, 177, no. 8 (2020):1735-1753,
https://doi.org/10.1111/bph.14930 . .

TY  - JOUR
AU  - Batinić, Bojan
AU  - Santrač, Anja
AU  - Divović, Branka
AU  - Timić, Tamara
AU  - Stanković, Tamara
AU  - Obradović, Aleksandar
AU  - Joksimović, Srđan
AU  - Savić, Miroslav
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2558
AB  - Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 mu g/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-alpha and IL-6 in dam blood withdrawn 2 h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5 mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively.
PB  - Elsevier Science BV, Amsterdam
T2  - Behavioural Brain Research
T1  - Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring
VL  - 299
SP  - 72
EP  - 80
DO  - 10.1016/j.bbr.2015.11.025
ER  - 

@article{
author = "Batinić, Bojan and Santrač, Anja and Divović, Branka and Timić, Tamara and Stanković, Tamara and Obradović, Aleksandar and Joksimović, Srđan and Savić, Miroslav",
year = "2016",
abstract = "Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 mu g/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-alpha and IL-6 in dam blood withdrawn 2 h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5 mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Behavioural Brain Research",
title = "Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring",
volume = "299",
pages = "72-80",
doi = "10.1016/j.bbr.2015.11.025"
}

Batinić, B., Santrač, A., Divović, B., Timić, T., Stanković, T., Obradović, A., Joksimović, S.,& Savić, M.. (2016). Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring. in Behavioural Brain Research
Elsevier Science BV, Amsterdam., 299, 72-80.
https://doi.org/10.1016/j.bbr.2015.11.025

Batinić B, Santrač A, Divović B, Timić T, Stanković T, Obradović A, Joksimović S, Savić M. Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring. in Behavioural Brain Research. 2016;299:72-80.
doi:10.1016/j.bbr.2015.11.025 .

Batinić, Bojan, Santrač, Anja, Divović, Branka, Timić, Tamara, Stanković, Tamara, Obradović, Aleksandar, Joksimović, Srđan, Savić, Miroslav, "Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring" in Behavioural Brain Research, 299 (2016):72-80,
https://doi.org/10.1016/j.bbr.2015.11.025 . .

TY  - JOUR
AU  - Timić-Stamenić, Tamara
AU  - Joksimović, Srđan
AU  - Biawat, Poonam
AU  - Stanković, Tamara
AU  - Marković, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2314
AB  - Reportedly, negative modulation of alpha(5) GABA(A) receptors may improve cognition in normal and pharmacologically-impaired animals, and such modulation has been proposed as an avenue for treatment of cognitive symptoms in schizophrenia. This study assessed the actions of PWZ-029, administered at doses (2, 5, and 10 mg/kg) at which it reached micromolar concentrations in brain tissue with estimated free concentrations adequate for selective modulation of alpha(5) GABA(A) receptors, in three cognitive tasks in male Wistar rats acutely treated with the noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801 (0.1 mg/kg), as well in tests of locomotor activity potentiated by MK-801 (0.2 mg/kg) or amphetamine (0.5 mg/kg). In a hormetic-like manner, only 5 mg/kg PWZ-029 reversed MK-801-induced deficits in novel object recognition test (visual recognition memory), whereas in the Morris water maze, the 2 mg/kg dose of PWZ-029 exerted partial beneficial effects on spatial learning impairment. PWZ-029 did not affect recognition memory deficits in social novelty discrimination procedure. Motor hyperactivity induced with MK-801 or amphetamine was not preventable by PWZ-029. Our results show that certain MK-801-induced memory deficits can be ameliorated by negative modulation of alpha(5) GABA(A) receptors, and point to the need for further elucidation of their translational relevance to cognitive deterioration in schizophrenia.
PB  - Sage Publications Ltd, London
T2  - Journal of Psychopharmacology
T1  - Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion
VL  - 29
IS  - 9
SP  - 1013
EP  - 1024
DO  - 10.1177/0269881115590601
ER  - 

@article{
author = "Timić-Stamenić, Tamara and Joksimović, Srđan and Biawat, Poonam and Stanković, Tamara and Marković, Bojan and Cook, James M. and Savić, Miroslav",
year = "2015",
abstract = "Reportedly, negative modulation of alpha(5) GABA(A) receptors may improve cognition in normal and pharmacologically-impaired animals, and such modulation has been proposed as an avenue for treatment of cognitive symptoms in schizophrenia. This study assessed the actions of PWZ-029, administered at doses (2, 5, and 10 mg/kg) at which it reached micromolar concentrations in brain tissue with estimated free concentrations adequate for selective modulation of alpha(5) GABA(A) receptors, in three cognitive tasks in male Wistar rats acutely treated with the noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801 (0.1 mg/kg), as well in tests of locomotor activity potentiated by MK-801 (0.2 mg/kg) or amphetamine (0.5 mg/kg). In a hormetic-like manner, only 5 mg/kg PWZ-029 reversed MK-801-induced deficits in novel object recognition test (visual recognition memory), whereas in the Morris water maze, the 2 mg/kg dose of PWZ-029 exerted partial beneficial effects on spatial learning impairment. PWZ-029 did not affect recognition memory deficits in social novelty discrimination procedure. Motor hyperactivity induced with MK-801 or amphetamine was not preventable by PWZ-029. Our results show that certain MK-801-induced memory deficits can be ameliorated by negative modulation of alpha(5) GABA(A) receptors, and point to the need for further elucidation of their translational relevance to cognitive deterioration in schizophrenia.",
publisher = "Sage Publications Ltd, London",
journal = "Journal of Psychopharmacology",
title = "Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion",
volume = "29",
number = "9",
pages = "1013-1024",
doi = "10.1177/0269881115590601"
}

Timić-Stamenić, T., Joksimović, S., Biawat, P., Stanković, T., Marković, B., Cook, J. M.,& Savić, M.. (2015). Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion. in Journal of Psychopharmacology
Sage Publications Ltd, London., 29(9), 1013-1024.
https://doi.org/10.1177/0269881115590601

Timić-Stamenić T, Joksimović S, Biawat P, Stanković T, Marković B, Cook JM, Savić M. Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion. in Journal of Psychopharmacology. 2015;29(9):1013-1024.
doi:10.1177/0269881115590601 .

Timić-Stamenić, Tamara, Joksimović, Srđan, Biawat, Poonam, Stanković, Tamara, Marković, Bojan, Cook, James M., Savić, Miroslav, "Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion" in Journal of Psychopharmacology, 29, no. 9 (2015):1013-1024,
https://doi.org/10.1177/0269881115590601 . .

TY  - CONF
AU  - Timić-Stamenić, Tamara
AU  - Joksimović, Srđan
AU  - Milić, Marija
AU  - Batinić, Bojan
AU  - Poe, Michael M.
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2106
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats
VL  - 24
IS  - Supplement 2
SP  - S325
EP  - S325
DO  - 10.1016/S0924-977X(14)70516-4
ER  - 

@conference{
author = "Timić-Stamenić, Tamara and Joksimović, Srđan and Milić, Marija and Batinić, Bojan and Poe, Michael M. and Cook, James M. and Savić, Miroslav",
year = "2014",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats",
volume = "24",
number = "Supplement 2",
pages = "S325-S325",
doi = "10.1016/S0924-977X(14)70516-4"
}

Timić-Stamenić, T., Joksimović, S., Milić, M., Batinić, B., Poe, M. M., Cook, J. M.,& Savić, M.. (2014). Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 24(Supplement 2), S325-S325.
https://doi.org/10.1016/S0924-977X(14)70516-4

Timić-Stamenić T, Joksimović S, Milić M, Batinić B, Poe MM, Cook JM, Savić M. Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats. in European Neuropsychopharmacology. 2014;24(Supplement 2):S325-S325.
doi:10.1016/S0924-977X(14)70516-4 .

Timić-Stamenić, Tamara, Joksimović, Srđan, Milić, Marija, Batinić, Bojan, Poe, Michael M., Cook, James M., Savić, Miroslav, "Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats" in European Neuropsychopharmacology, 24, no. Supplement 2 (2014):S325-S325,
https://doi.org/10.1016/S0924-977X(14)70516-4 . .

TY  - JOUR
AU  - Kovacević, Jovana
AU  - Timić, Tamara
AU  - Tiruveedhula, Veera V.
AU  - Batinić, Bojan
AU  - Namjoshi, Ojas A.
AU  - Milić, Marija
AU  - Joksimović, Srđan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2205
AB  - Long-term use of benzodiazepine-type drugs may lead to physical dependence, manifested by withdrawal syndrome after abrupt cessation of treatment. The aim of the present study was to investigate the influence of duration of treatment, as well as the role of alpha(1)-containing GABA(A) receptors, in development of physical dependence to diazepam, assessed through the level of anxiety and susceptibility to pentylenetetrazole (PTZ)-induced seizures, 24 h after withdrawal from protracted treatment in rats. Withdrawal of 2 mg/kg diazepam after 28, but not after 14 or 21 days of administration led to an anxiety-like behavior in the elevated plus maze. Antagonism of the diazepam effects at alpha(1)-containing GABA(A) receptors, achieved by daily administration of the neutral modulator beta CCt (5 mg/kg), did not affect the anxiety level during withdrawal. An increased susceptibility to PTZ-induced seizures was observed during diazepam withdrawal after 21 and 28 days of treatment. Daily co-administration of beta CCt further decreased the PTZ-seizure threshold after 21 days of treatment, whilst it prevented the diazepam withdrawal-elicited decrease of the PTZ threshold after 28 days of treatment. In conclusion, the current study suggests that the role of alpha(1)-containing GABA(A) receptors in mediating the development of physical dependence may vary based on the effect being studied and duration of protracted treatment. Moreover, the present data supports previous findings that the lack of activity at alpha(1)-containing GABA(A) receptors is not sufficient to eliminate physical dependence liability of ligands of the benzodiazepine type.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Brain Research Bulletin
T1  - Duration of treatment and activation of alpha(1)-containing GABA(A) receptors variably affect the level of anxiety and seizure susceptibility after diazepam withdrawal in rats
VL  - 104
SP  - 1
EP  - 6
DO  - 10.1016/j.brainresbull.2014.03.002
ER  - 

@article{
author = "Kovacević, Jovana and Timić, Tamara and Tiruveedhula, Veera V. and Batinić, Bojan and Namjoshi, Ojas A. and Milić, Marija and Joksimović, Srđan and Cook, James M. and Savić, Miroslav",
year = "2014",
abstract = "Long-term use of benzodiazepine-type drugs may lead to physical dependence, manifested by withdrawal syndrome after abrupt cessation of treatment. The aim of the present study was to investigate the influence of duration of treatment, as well as the role of alpha(1)-containing GABA(A) receptors, in development of physical dependence to diazepam, assessed through the level of anxiety and susceptibility to pentylenetetrazole (PTZ)-induced seizures, 24 h after withdrawal from protracted treatment in rats. Withdrawal of 2 mg/kg diazepam after 28, but not after 14 or 21 days of administration led to an anxiety-like behavior in the elevated plus maze. Antagonism of the diazepam effects at alpha(1)-containing GABA(A) receptors, achieved by daily administration of the neutral modulator beta CCt (5 mg/kg), did not affect the anxiety level during withdrawal. An increased susceptibility to PTZ-induced seizures was observed during diazepam withdrawal after 21 and 28 days of treatment. Daily co-administration of beta CCt further decreased the PTZ-seizure threshold after 21 days of treatment, whilst it prevented the diazepam withdrawal-elicited decrease of the PTZ threshold after 28 days of treatment. In conclusion, the current study suggests that the role of alpha(1)-containing GABA(A) receptors in mediating the development of physical dependence may vary based on the effect being studied and duration of protracted treatment. Moreover, the present data supports previous findings that the lack of activity at alpha(1)-containing GABA(A) receptors is not sufficient to eliminate physical dependence liability of ligands of the benzodiazepine type.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Brain Research Bulletin",
title = "Duration of treatment and activation of alpha(1)-containing GABA(A) receptors variably affect the level of anxiety and seizure susceptibility after diazepam withdrawal in rats",
volume = "104",
pages = "1-6",
doi = "10.1016/j.brainresbull.2014.03.002"
}

Kovacević, J., Timić, T., Tiruveedhula, V. V., Batinić, B., Namjoshi, O. A., Milić, M., Joksimović, S., Cook, J. M.,& Savić, M.. (2014). Duration of treatment and activation of alpha(1)-containing GABA(A) receptors variably affect the level of anxiety and seizure susceptibility after diazepam withdrawal in rats. in Brain Research Bulletin
Pergamon-Elsevier Science Ltd, Oxford., 104, 1-6.
https://doi.org/10.1016/j.brainresbull.2014.03.002

Kovacević J, Timić T, Tiruveedhula VV, Batinić B, Namjoshi OA, Milić M, Joksimović S, Cook JM, Savić M. Duration of treatment and activation of alpha(1)-containing GABA(A) receptors variably affect the level of anxiety and seizure susceptibility after diazepam withdrawal in rats. in Brain Research Bulletin. 2014;104:1-6.
doi:10.1016/j.brainresbull.2014.03.002 .

Kovacević, Jovana, Timić, Tamara, Tiruveedhula, Veera V., Batinić, Bojan, Namjoshi, Ojas A., Milić, Marija, Joksimović, Srđan, Cook, James M., Savić, Miroslav, "Duration of treatment and activation of alpha(1)-containing GABA(A) receptors variably affect the level of anxiety and seizure susceptibility after diazepam withdrawal in rats" in Brain Research Bulletin, 104 (2014):1-6,
https://doi.org/10.1016/j.brainresbull.2014.03.002 . .

TY  - JOUR
AU  - Obradović, Aleksandar
AU  - Joksimović, Srđan
AU  - Poe, Michael M.
AU  - Ramerstorfer, Joachim
AU  - Varagić, Zdravko
AU  - Namjoshi, Ojas A.
AU  - Batinić, Bojan
AU  - Radulović, Tamara
AU  - Marković, Bojan
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2200
AB  - Enormous progress in understanding the role of four populations of benzodiazepine-sensitive GABA(A) receptors was paralleled by the puzzling findings suggesting that substantial separation of behavioral effects may be accomplished by apparently nonselective modulators. We report on SH-I-048A, a newly synthesized chiral positive modulator of GABAA receptors characterized by exceptional subnanomolar affinity, high efficacy and non-selectivity. Its influence on behavior was assessed in Wistar rats and contrasted to that obtained with 2 mg/kg diazepam. SH-I-048A reached micromolar concentrations in brain tissue, while the unbound fraction in brain homogenate was around 1.5%. The approximated electrophysiological responses, which estimated free concentrations of SH-I-048A or diazepam are able to elicit, suggested a similarity between the 10 mg/kg dose of the novel ligand and 2 mg/kg diazepam; however, SH-I-048A was relatively more active at and as-containing GABAA receptors. Behaviorally, SH-I-048A induced sedative, muscle relaxant and ataxic effects, reversed mechanical hyperalgesia 24 h after injury, while it was devoid of clear anxiolytic actions and did not affect water-maze performance. While lack of clear anxiolytic actions may be connected with an enhanced potentiation at al-containing GABAA receptors, the observed behavior in the rotarod, water maze and peripheral nerve injury tests was possibly affected by its prominent action at receptors containing the as subunit. The current results encourage further innovative approaches aimed at linking in vitro an in vivo data in order to help define fine-tuning mechanisms at four sensitive receptor populations that underlie subtle differences in behavioral profiles of benzodiazepine site ligands.
PB  - Elsevier Science BV, Amsterdam
T2  - Brain Research
T1  - Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects
VL  - 1554
SP  - 36
EP  - 48
DO  - 10.1016/j.brainres.2014.01.036
ER  - 

@article{
author = "Obradović, Aleksandar and Joksimović, Srđan and Poe, Michael M. and Ramerstorfer, Joachim and Varagić, Zdravko and Namjoshi, Ojas A. and Batinić, Bojan and Radulović, Tamara and Marković, Bojan and Roth, Brian L. and Sieghart, Werner and Cook, James M. and Savić, Miroslav",
year = "2014",
abstract = "Enormous progress in understanding the role of four populations of benzodiazepine-sensitive GABA(A) receptors was paralleled by the puzzling findings suggesting that substantial separation of behavioral effects may be accomplished by apparently nonselective modulators. We report on SH-I-048A, a newly synthesized chiral positive modulator of GABAA receptors characterized by exceptional subnanomolar affinity, high efficacy and non-selectivity. Its influence on behavior was assessed in Wistar rats and contrasted to that obtained with 2 mg/kg diazepam. SH-I-048A reached micromolar concentrations in brain tissue, while the unbound fraction in brain homogenate was around 1.5%. The approximated electrophysiological responses, which estimated free concentrations of SH-I-048A or diazepam are able to elicit, suggested a similarity between the 10 mg/kg dose of the novel ligand and 2 mg/kg diazepam; however, SH-I-048A was relatively more active at and as-containing GABAA receptors. Behaviorally, SH-I-048A induced sedative, muscle relaxant and ataxic effects, reversed mechanical hyperalgesia 24 h after injury, while it was devoid of clear anxiolytic actions and did not affect water-maze performance. While lack of clear anxiolytic actions may be connected with an enhanced potentiation at al-containing GABAA receptors, the observed behavior in the rotarod, water maze and peripheral nerve injury tests was possibly affected by its prominent action at receptors containing the as subunit. The current results encourage further innovative approaches aimed at linking in vitro an in vivo data in order to help define fine-tuning mechanisms at four sensitive receptor populations that underlie subtle differences in behavioral profiles of benzodiazepine site ligands.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Brain Research",
title = "Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects",
volume = "1554",
pages = "36-48",
doi = "10.1016/j.brainres.2014.01.036"
}

Obradović, A., Joksimović, S., Poe, M. M., Ramerstorfer, J., Varagić, Z., Namjoshi, O. A., Batinić, B., Radulović, T., Marković, B., Roth, B. L., Sieghart, W., Cook, J. M.,& Savić, M.. (2014). Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects. in Brain Research
Elsevier Science BV, Amsterdam., 1554, 36-48.
https://doi.org/10.1016/j.brainres.2014.01.036

Obradović A, Joksimović S, Poe MM, Ramerstorfer J, Varagić Z, Namjoshi OA, Batinić B, Radulović T, Marković B, Roth BL, Sieghart W, Cook JM, Savić M. Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects. in Brain Research. 2014;1554:36-48.
doi:10.1016/j.brainres.2014.01.036 .

Obradović, Aleksandar, Joksimović, Srđan, Poe, Michael M., Ramerstorfer, Joachim, Varagić, Zdravko, Namjoshi, Ojas A., Batinić, Bojan, Radulović, Tamara, Marković, Bojan, Roth, Brian L., Sieghart, Werner, Cook, James M., Savić, Miroslav, "Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects" in Brain Research, 1554 (2014):36-48,
https://doi.org/10.1016/j.brainres.2014.01.036 . .

TY  - JOUR
AU  - Obradović, Aleksandar
AU  - Joksimović, Srđan
AU  - Michael, Poe M.
AU  - Timić, Tamara
AU  - James, Cook M.
AU  - Savić, Miroslav
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2284
AB  - The complex clinical picture of mono-neuropathy following injury of peripheral nerve is often accompanied by changes in the patients' affective states. It has been shown that positive allosteric modulators of GABAA receptors can decrease nociceptive transmission in animal pain models. However, recent findings suggest a possibility that at least some of the antinociceptive effects of benzodiazepines, related to neuropathic painful stimuli, may to a significant degree be a consequence of their anxiolytic action. In this study we evaluated the possible delayed effects of SH-I-048A, a newly- synthesized high-efficacy nonselective positive modulator of GABAA receptors, on anxiety-like behavior and locomotor activity in Wistar rats with a previously induced peripheral nerve injury. Assessment of behavioral parameters, using spontaneous locomotor activity and elevated plus maze tests, was performed 48h after completion of single-day three i.p. injections treatment consisting of zero, one, two or three doses of SH-I-048A (10 mg/kg). In general, rats' behavior observed 72 h after a moderate peripheral nerve injury did not indicate the persistence of sequelae of mono-neuropathic pain. The rats treated with three doses of SH-I-048A displayed an enhanced immobility time in the locomotor activity test, without concomitant decrease of the total distance traveled. On the other hand, in the group treated with two doses of SH-I-048A, a decrease in the emotional reactivity in the elevated plus maze test was observed. Subtle changes in the regimen of dosing of SH-I-048A affect locomotor activity and anxiety-related behavior in animals with peripheral nerve injury.
AB  - Kompleksna klinička slika neuropatije nakon povrede perifernog nerva često je praćena i promenama afektivnog stanja pacijenata. U animalnim modelima bola pokazano je da pozitivni alosterni modulatori GABAA receptora mogu da smanje nociceptivnu transmisiju. Međutim, skorašnji nalazi ukazuju i na mogućnost da je prividni antinociceptivni efekat benzodiazepina nakon delovanja akutnog bolnog stimulusa u značajnoj meri posledica anksiolitičnog efekta. U ovoj studiji ispitani su mogući odloženi efekti novosintetisanog, neselektivnog liganda GABAA receptora (SH-I-048A) na lokomotornu aktivnost i ponašanje u vezi sa anksioznošću kod pacova soja Wistar prethodno podvrgnutih povredi perifernog nerva. Procena bihejvioralnih parametara sprovedena je testovima spontane lokomotorne aktivnosti i uzdignutog plus lavirinta 48 sati nakon što su životinje u periodu od 24 sata primile rastvarač, jednu, dve ili tri doze SH-I-048A (10 mg/kg). Generalno, ponašanje pacova praćeno 72 sata nakon umerene povrede perifernog nerva nije ukazivalo na prisustvo perzistentnih posledica neuropatskog bola. Pacovi prethodno tretirani sa tri doze SH-I-048A ispoljili su povećano vreme imobilnosti u testu lokomotorne aktivnosti, bez značajnog smanjenja ukupnog pređenog puta. S druge strane, u grupi koja je tretirana sa dve doze SH-I-048A zapažena je smanjena emocionalna reaktivnost u uzdignutom plus lavirintu. Kod životinja sa povredom perifernog nerva, suptilne razlike u režimu doziranja pozitivnog modulatora GABAA, mogu značajno da utiču na ponašanje vezano za lomotornu aktivnost i nivo anksioznosti.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria
T1  - Delayed behavioral effects of SH-I-048A, a novel nonselective positive modulator of GABAA receptors, after peripheral nerve injury in rats
T1  - Odloženi bihejvioralni efekti SH-I-048A, novog neselektivnog pozitivnog modulatora GABAA receptora, nakon povrede perifernog nerva pacova
VL  - 64
IS  - 2
SP  - 189
EP  - 199
DO  - 10.2478/acve-2014-0018
ER  - 

@article{
author = "Obradović, Aleksandar and Joksimović, Srđan and Michael, Poe M. and Timić, Tamara and James, Cook M. and Savić, Miroslav",
year = "2014",
abstract = "The complex clinical picture of mono-neuropathy following injury of peripheral nerve is often accompanied by changes in the patients' affective states. It has been shown that positive allosteric modulators of GABAA receptors can decrease nociceptive transmission in animal pain models. However, recent findings suggest a possibility that at least some of the antinociceptive effects of benzodiazepines, related to neuropathic painful stimuli, may to a significant degree be a consequence of their anxiolytic action. In this study we evaluated the possible delayed effects of SH-I-048A, a newly- synthesized high-efficacy nonselective positive modulator of GABAA receptors, on anxiety-like behavior and locomotor activity in Wistar rats with a previously induced peripheral nerve injury. Assessment of behavioral parameters, using spontaneous locomotor activity and elevated plus maze tests, was performed 48h after completion of single-day three i.p. injections treatment consisting of zero, one, two or three doses of SH-I-048A (10 mg/kg). In general, rats' behavior observed 72 h after a moderate peripheral nerve injury did not indicate the persistence of sequelae of mono-neuropathic pain. The rats treated with three doses of SH-I-048A displayed an enhanced immobility time in the locomotor activity test, without concomitant decrease of the total distance traveled. On the other hand, in the group treated with two doses of SH-I-048A, a decrease in the emotional reactivity in the elevated plus maze test was observed. Subtle changes in the regimen of dosing of SH-I-048A affect locomotor activity and anxiety-related behavior in animals with peripheral nerve injury., Kompleksna klinička slika neuropatije nakon povrede perifernog nerva često je praćena i promenama afektivnog stanja pacijenata. U animalnim modelima bola pokazano je da pozitivni alosterni modulatori GABAA receptora mogu da smanje nociceptivnu transmisiju. Međutim, skorašnji nalazi ukazuju i na mogućnost da je prividni antinociceptivni efekat benzodiazepina nakon delovanja akutnog bolnog stimulusa u značajnoj meri posledica anksiolitičnog efekta. U ovoj studiji ispitani su mogući odloženi efekti novosintetisanog, neselektivnog liganda GABAA receptora (SH-I-048A) na lokomotornu aktivnost i ponašanje u vezi sa anksioznošću kod pacova soja Wistar prethodno podvrgnutih povredi perifernog nerva. Procena bihejvioralnih parametara sprovedena je testovima spontane lokomotorne aktivnosti i uzdignutog plus lavirinta 48 sati nakon što su životinje u periodu od 24 sata primile rastvarač, jednu, dve ili tri doze SH-I-048A (10 mg/kg). Generalno, ponašanje pacova praćeno 72 sata nakon umerene povrede perifernog nerva nije ukazivalo na prisustvo perzistentnih posledica neuropatskog bola. Pacovi prethodno tretirani sa tri doze SH-I-048A ispoljili su povećano vreme imobilnosti u testu lokomotorne aktivnosti, bez značajnog smanjenja ukupnog pređenog puta. S druge strane, u grupi koja je tretirana sa dve doze SH-I-048A zapažena je smanjena emocionalna reaktivnost u uzdignutom plus lavirintu. Kod životinja sa povredom perifernog nerva, suptilne razlike u režimu doziranja pozitivnog modulatora GABAA, mogu značajno da utiču na ponašanje vezano za lomotornu aktivnost i nivo anksioznosti.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria",
title = "Delayed behavioral effects of SH-I-048A, a novel nonselective positive modulator of GABAA receptors, after peripheral nerve injury in rats, Odloženi bihejvioralni efekti SH-I-048A, novog neselektivnog pozitivnog modulatora GABAA receptora, nakon povrede perifernog nerva pacova",
volume = "64",
number = "2",
pages = "189-199",
doi = "10.2478/acve-2014-0018"
}

Obradović, A., Joksimović, S., Michael, P. M., Timić, T., James, C. M.,& Savić, M.. (2014). Delayed behavioral effects of SH-I-048A, a novel nonselective positive modulator of GABAA receptors, after peripheral nerve injury in rats. in Acta veterinaria
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 64(2), 189-199.
https://doi.org/10.2478/acve-2014-0018

Obradović A, Joksimović S, Michael PM, Timić T, James CM, Savić M. Delayed behavioral effects of SH-I-048A, a novel nonselective positive modulator of GABAA receptors, after peripheral nerve injury in rats. in Acta veterinaria. 2014;64(2):189-199.
doi:10.2478/acve-2014-0018 .

Obradović, Aleksandar, Joksimović, Srđan, Michael, Poe M., Timić, Tamara, James, Cook M., Savić, Miroslav, "Delayed behavioral effects of SH-I-048A, a novel nonselective positive modulator of GABAA receptors, after peripheral nerve injury in rats" in Acta veterinaria, 64, no. 2 (2014):189-199,
https://doi.org/10.2478/acve-2014-0018 . .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Obradović, Aleksandar
AU  - Timić, Tamara
AU  - Radulović, Tamara
AU  - Biawat, Poonam
AU  - Kovacević, Jovana
AU  - Milić, Marija
AU  - Batinić, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1888
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia
VL  - 23
IS  - Supplement 2
SP  - S260
EP  - S260
DO  - 10.1016/S0924-977X(13)70406-1
ER  - 

@conference{
author = "Joksimović, Srđan and Obradović, Aleksandar and Timić, Tamara and Radulović, Tamara and Biawat, Poonam and Kovacević, Jovana and Milić, Marija and Batinić, Bojan and Cook, James M. and Savić, Miroslav",
year = "2013",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia",
volume = "23",
number = "Supplement 2",
pages = "S260-S260",
doi = "10.1016/S0924-977X(13)70406-1"
}

Joksimović, S., Obradović, A., Timić, T., Radulović, T., Biawat, P., Kovacević, J., Milić, M., Batinić, B., Cook, J. M.,& Savić, M.. (2013). PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 23(Supplement 2), S260-S260.
https://doi.org/10.1016/S0924-977X(13)70406-1

Joksimović S, Obradović A, Timić T, Radulović T, Biawat P, Kovacević J, Milić M, Batinić B, Cook JM, Savić M. PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia. in European Neuropsychopharmacology. 2013;23(Supplement 2):S260-S260.
doi:10.1016/S0924-977X(13)70406-1 .

Joksimović, Srđan, Obradović, Aleksandar, Timić, Tamara, Radulović, Tamara, Biawat, Poonam, Kovacević, Jovana, Milić, Marija, Batinić, Bojan, Cook, James M., Savić, Miroslav, "PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia" in European Neuropsychopharmacology, 23, no. Supplement 2 (2013):S260-S260,
https://doi.org/10.1016/S0924-977X(13)70406-1 . .

TY  - CONF
AU  - Timić, Tamara
AU  - Joksimović, Srđan
AU  - Obradović, Aleksandar
AU  - Poe, Michael M.
AU  - Biawat, Poonam
AU  - Ramerstorfer, Joachim
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1887
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors
VL  - 23
IS  - Supplement 2
SP  - S259
EP  - S260
DO  - 10.1016/S0924-977X(13)70405-X
ER  - 

@conference{
author = "Timić, Tamara and Joksimović, Srđan and Obradović, Aleksandar and Poe, Michael M. and Biawat, Poonam and Ramerstorfer, Joachim and Roth, Brian L. and Sieghart, Werner and Cook, James M. and Savić, Miroslav",
year = "2013",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors",
volume = "23",
number = "Supplement 2",
pages = "S259-S260",
doi = "10.1016/S0924-977X(13)70405-X"
}

Timić, T., Joksimović, S., Obradović, A., Poe, M. M., Biawat, P., Ramerstorfer, J., Roth, B. L., Sieghart, W., Cook, J. M.,& Savić, M.. (2013). MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 23(Supplement 2), S259-S260.
https://doi.org/10.1016/S0924-977X(13)70405-X

Timić T, Joksimović S, Obradović A, Poe MM, Biawat P, Ramerstorfer J, Roth BL, Sieghart W, Cook JM, Savić M. MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors. in European Neuropsychopharmacology. 2013;23(Supplement 2):S259-S260.
doi:10.1016/S0924-977X(13)70405-X .

Timić, Tamara, Joksimović, Srđan, Obradović, Aleksandar, Poe, Michael M., Biawat, Poonam, Ramerstorfer, Joachim, Roth, Brian L., Sieghart, Werner, Cook, James M., Savić, Miroslav, "MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors" in European Neuropsychopharmacology, 23, no. Supplement 2 (2013):S259-S260,
https://doi.org/10.1016/S0924-977X(13)70405-X . .

TY  - JOUR
AU  - Joksimović, Srđan
AU  - Divljaković, Jovana
AU  - van Linn, Michael
AU  - Varagić, Zdravko
AU  - Brajković, Gordana
AU  - Milinković, Marija M.
AU  - Yin, Wenyuan
AU  - Timić, Tamara
AU  - Sieghart, Werner
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2028
AB  - Despite significant advances in understanding the role of benzodiazepine (BZ)-sensitive populations of GABA A receptors, containing the α 1 , α 2 , α 3 or α 5 subunit, factual substrates of BZ-induced learning and memory deficits are not yet fully elucidated. It was shown that α 1 -subunit affinity-selective antagonist Β-CCt almost completely abolished spatial learning deficits induced by diazepam (DZP) in the Morris water maze. We examined a novel, highly (105 fold) α 1 -subunit selective ligand-WYS8 (0.2, 1 and 10mg/kg), on its own and in combination with the non-selective agonist DZP (2mg/kg) or Β-CCt (5mg/kg) in the water maze in rats. The in vitro efficacy study revealed that WYS8 acts as α 1 -subtype selective weak partial positive modulator (40% potentiation at 100nM). Measurement of concentrations of WYS8 and DZP in rat serum and brain tissues suggested that they did not substantially cross-influence the respective disposition. In the water maze, DZP impaired spatial learning (acquisition trials) and memory (probe trial). WYS8 caused no effect per se, did not affect the overall influence of DZP on the water-maze performance and was devoid of any activity in this task when combined with Β-CCt. Nonetheless, an additional analysis of the latency to reach the platform and the total distance swam suggested that WYS8 addition attenuated the run-down of the spatial impairment induced by DZP at the end of acquisition trials. These results demonstrate a clear difference in the influence of an α 1 subtype-selective antagonist and a partial agonist on the effects of DZP on the water-maze acquisition.
T2  - European Neuropsychopharmacology
T1  - Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors
VL  - 23
IS  - 5
SP  - 390
EP  - 399
DO  - 10.1016/j.euroneuro.2012.05.003
ER  - 

@article{
author = "Joksimović, Srđan and Divljaković, Jovana and van Linn, Michael and Varagić, Zdravko and Brajković, Gordana and Milinković, Marija M. and Yin, Wenyuan and Timić, Tamara and Sieghart, Werner and Cook, James M. and Savić, Miroslav",
year = "2013",
abstract = "Despite significant advances in understanding the role of benzodiazepine (BZ)-sensitive populations of GABA A receptors, containing the α 1 , α 2 , α 3 or α 5 subunit, factual substrates of BZ-induced learning and memory deficits are not yet fully elucidated. It was shown that α 1 -subunit affinity-selective antagonist Β-CCt almost completely abolished spatial learning deficits induced by diazepam (DZP) in the Morris water maze. We examined a novel, highly (105 fold) α 1 -subunit selective ligand-WYS8 (0.2, 1 and 10mg/kg), on its own and in combination with the non-selective agonist DZP (2mg/kg) or Β-CCt (5mg/kg) in the water maze in rats. The in vitro efficacy study revealed that WYS8 acts as α 1 -subtype selective weak partial positive modulator (40% potentiation at 100nM). Measurement of concentrations of WYS8 and DZP in rat serum and brain tissues suggested that they did not substantially cross-influence the respective disposition. In the water maze, DZP impaired spatial learning (acquisition trials) and memory (probe trial). WYS8 caused no effect per se, did not affect the overall influence of DZP on the water-maze performance and was devoid of any activity in this task when combined with Β-CCt. Nonetheless, an additional analysis of the latency to reach the platform and the total distance swam suggested that WYS8 addition attenuated the run-down of the spatial impairment induced by DZP at the end of acquisition trials. These results demonstrate a clear difference in the influence of an α 1 subtype-selective antagonist and a partial agonist on the effects of DZP on the water-maze acquisition.",
journal = "European Neuropsychopharmacology",
title = "Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors",
volume = "23",
number = "5",
pages = "390-399",
doi = "10.1016/j.euroneuro.2012.05.003"
}

Joksimović, S., Divljaković, J., van Linn, M., Varagić, Z., Brajković, G., Milinković, M. M., Yin, W., Timić, T., Sieghart, W., Cook, J. M.,& Savić, M.. (2013). Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors. in European Neuropsychopharmacology, 23(5), 390-399.
https://doi.org/10.1016/j.euroneuro.2012.05.003

Joksimović S, Divljaković J, van Linn M, Varagić Z, Brajković G, Milinković MM, Yin W, Timić T, Sieghart W, Cook JM, Savić M. Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors. in European Neuropsychopharmacology. 2013;23(5):390-399.
doi:10.1016/j.euroneuro.2012.05.003 .

Joksimović, Srđan, Divljaković, Jovana, van Linn, Michael, Varagić, Zdravko, Brajković, Gordana, Milinković, Marija M., Yin, Wenyuan, Timić, Tamara, Sieghart, Werner, Cook, James M., Savić, Miroslav, "Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors" in European Neuropsychopharmacology, 23, no. 5 (2013):390-399,
https://doi.org/10.1016/j.euroneuro.2012.05.003 . .

TY  - JOUR
AU  - Milić, Marija
AU  - Timić, Tamara
AU  - Joksimović, Srđan
AU  - Biawat, Poonam
AU  - Rallapalli, Sundari
AU  - Divljaković, Jovana
AU  - Radulović, Tamara
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1926
AB  - Inverse agonism at the benzodiazepine site of alpha(5) subunit-containing GABA(A) receptors is an attractive approach for the development of putative cognition-enhancing compounds, which are still far from clinical application. Several ligands with binding and/or functional selectivity for alpha(5) GABA(A) receptors have been synthesized and tested in a few animal models. PWZ-029 is an alpha(5) GABA(A) selective inverse agonist whose memory enhancing effects were demonstrated in the passive avoidance task in rats and in Pavlovian fear conditioning in mice. In the present study we investigated the effects of PWZ-029 administration in novel object recognition test and Morris water maze, in normal and scopolamine-treated rats. All the three doses of PWZ-029 (2,5 and 10 mg/kg) improved object recognition after the 24-h delay period, as shown by significant differences between the exploration times of the novel and old object, and the respective discrimination indices. PWZ-029 (2 mg/kg) also successfully reversed the 0.3 mg/kg scopolamine-induced deficit in recognition memory after the 1-h delay. In the Morris water maze test, PWZ-029 (5,10 and 15 mg/kg) did not significantly influence swim patterns, either during five acquisition days or during the treatment-free probe trial. PWZ-029 (2, 5 and 10 mg/kg) also proved to be ineffective in the reversal of the 1 mg/kg scopolamine-induced memory impairment in the water maze. The present mixed results encourage use of a variety of tests and experimental conditions in order to increase the predictability of preclinical testing of selective as GABA(A) inverse agonists.
PB  - Elsevier Science BV, Amsterdam
T2  - Behavioural Brain Research
T1  - PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats
VL  - 241
SP  - 206
EP  - 213
DO  - 10.1016/j.bbr.2012.12.016
ER  - 

@article{
author = "Milić, Marija and Timić, Tamara and Joksimović, Srđan and Biawat, Poonam and Rallapalli, Sundari and Divljaković, Jovana and Radulović, Tamara and Cook, James M. and Savić, Miroslav",
year = "2013",
abstract = "Inverse agonism at the benzodiazepine site of alpha(5) subunit-containing GABA(A) receptors is an attractive approach for the development of putative cognition-enhancing compounds, which are still far from clinical application. Several ligands with binding and/or functional selectivity for alpha(5) GABA(A) receptors have been synthesized and tested in a few animal models. PWZ-029 is an alpha(5) GABA(A) selective inverse agonist whose memory enhancing effects were demonstrated in the passive avoidance task in rats and in Pavlovian fear conditioning in mice. In the present study we investigated the effects of PWZ-029 administration in novel object recognition test and Morris water maze, in normal and scopolamine-treated rats. All the three doses of PWZ-029 (2,5 and 10 mg/kg) improved object recognition after the 24-h delay period, as shown by significant differences between the exploration times of the novel and old object, and the respective discrimination indices. PWZ-029 (2 mg/kg) also successfully reversed the 0.3 mg/kg scopolamine-induced deficit in recognition memory after the 1-h delay. In the Morris water maze test, PWZ-029 (5,10 and 15 mg/kg) did not significantly influence swim patterns, either during five acquisition days or during the treatment-free probe trial. PWZ-029 (2, 5 and 10 mg/kg) also proved to be ineffective in the reversal of the 1 mg/kg scopolamine-induced memory impairment in the water maze. The present mixed results encourage use of a variety of tests and experimental conditions in order to increase the predictability of preclinical testing of selective as GABA(A) inverse agonists.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Behavioural Brain Research",
title = "PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats",
volume = "241",
pages = "206-213",
doi = "10.1016/j.bbr.2012.12.016"
}

Milić, M., Timić, T., Joksimović, S., Biawat, P., Rallapalli, S., Divljaković, J., Radulović, T., Cook, J. M.,& Savić, M.. (2013). PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats. in Behavioural Brain Research
Elsevier Science BV, Amsterdam., 241, 206-213.
https://doi.org/10.1016/j.bbr.2012.12.016

Milić M, Timić T, Joksimović S, Biawat P, Rallapalli S, Divljaković J, Radulović T, Cook JM, Savić M. PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats. in Behavioural Brain Research. 2013;241:206-213.
doi:10.1016/j.bbr.2012.12.016 .

Milić, Marija, Timić, Tamara, Joksimović, Srđan, Biawat, Poonam, Rallapalli, Sundari, Divljaković, Jovana, Radulović, Tamara, Cook, James M., Savić, Miroslav, "PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats" in Behavioural Brain Research, 241 (2013):206-213,
https://doi.org/10.1016/j.bbr.2012.12.016 . .

TY  - JOUR
AU  - Joksimović, Srđan
AU  - Varagić, Zdravko
AU  - Kovacević, Jovana
AU  - van Linn, Michael
AU  - Milić, Marija
AU  - Rallapalli, Sundari
AU  - Timić, Tamara
AU  - Sieghart, Werner
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1839
AB  - Synthesis of ligands inactive or with low activity at alpha(1) GABA(A) receptors has become the key concept for development of novel, more tolerable benzodiazepine (BZ)-like drugs. WYS8, a remarkably (105 times) alpha(1)-subtype selective partial positive modulator, may serve as a pharmacological tool for refining the role of alpha(1) GABA(A) receptors in mediation of BZs' effects. Here, the effects of WYS8 on GABA-induced currents and on diazepam-induced potentiation of recombinant BZ-sensitive GABA(A) receptors were studied in more detail. In addition, the behavioral profile of WYS8 (0.2, 1, and 10 mg/kg i.p.), on its own and in combination with diazepam, was tested in the spontaneous locomotor activity, elevated plus maze, grip strength, rotarod, and pentylenetetrazole tests. WYS8, applied at an in vivo attainable concentration of 100 nM, reduced the stimulation of GABA currents by 1 mu M diazepam by 57 % at alpha(1)beta(3)gamma(2), but not at alpha(2)beta(3)gamma(2), alpha(3)beta(3)gamma(2), or alpha(5)beta(3)gamma(2) GABA(A) receptors. The administration of WYS8 alone induced negligible behavioral consequences. When combined with diazepam, WYS8 caused a reduction in sedation, muscle relaxation, and anticonvulsant activity, as compared with this BZ alone, whereas ataxia was preserved, and the anxiolytic effect of 2 mg/kg diazepam was unmasked. Hence, a partial instead of full activation at alpha(1) GABA(A) receptors did not necessarily result in the attenuation of the effects assumed to be mediated by activation of these receptors, or in the full preservation of the effects mediated by activation of other GABA(A) receptors. Thus, the role of alpha(1) GABA(A) receptors appears more complex than that proposed by genetic studies.
PB  - Springer, New York
T2  - QSAR & Combinatorial Science
T1  - Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?
VL  - 230
IS  - 1
SP  - 113
EP  - 123
DO  - 10.1007/s00213-013-3143-4
ER  - 

@article{
author = "Joksimović, Srđan and Varagić, Zdravko and Kovacević, Jovana and van Linn, Michael and Milić, Marija and Rallapalli, Sundari and Timić, Tamara and Sieghart, Werner and Cook, James M. and Savić, Miroslav",
year = "2013",
abstract = "Synthesis of ligands inactive or with low activity at alpha(1) GABA(A) receptors has become the key concept for development of novel, more tolerable benzodiazepine (BZ)-like drugs. WYS8, a remarkably (105 times) alpha(1)-subtype selective partial positive modulator, may serve as a pharmacological tool for refining the role of alpha(1) GABA(A) receptors in mediation of BZs' effects. Here, the effects of WYS8 on GABA-induced currents and on diazepam-induced potentiation of recombinant BZ-sensitive GABA(A) receptors were studied in more detail. In addition, the behavioral profile of WYS8 (0.2, 1, and 10 mg/kg i.p.), on its own and in combination with diazepam, was tested in the spontaneous locomotor activity, elevated plus maze, grip strength, rotarod, and pentylenetetrazole tests. WYS8, applied at an in vivo attainable concentration of 100 nM, reduced the stimulation of GABA currents by 1 mu M diazepam by 57 % at alpha(1)beta(3)gamma(2), but not at alpha(2)beta(3)gamma(2), alpha(3)beta(3)gamma(2), or alpha(5)beta(3)gamma(2) GABA(A) receptors. The administration of WYS8 alone induced negligible behavioral consequences. When combined with diazepam, WYS8 caused a reduction in sedation, muscle relaxation, and anticonvulsant activity, as compared with this BZ alone, whereas ataxia was preserved, and the anxiolytic effect of 2 mg/kg diazepam was unmasked. Hence, a partial instead of full activation at alpha(1) GABA(A) receptors did not necessarily result in the attenuation of the effects assumed to be mediated by activation of these receptors, or in the full preservation of the effects mediated by activation of other GABA(A) receptors. Thus, the role of alpha(1) GABA(A) receptors appears more complex than that proposed by genetic studies.",
publisher = "Springer, New York",
journal = "QSAR & Combinatorial Science",
title = "Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?",
volume = "230",
number = "1",
pages = "113-123",
doi = "10.1007/s00213-013-3143-4"
}

Joksimović, S., Varagić, Z., Kovacević, J., van Linn, M., Milić, M., Rallapalli, S., Timić, T., Sieghart, W., Cook, J. M.,& Savić, M.. (2013). Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?. in QSAR & Combinatorial Science
Springer, New York., 230(1), 113-123.
https://doi.org/10.1007/s00213-013-3143-4

Joksimović S, Varagić Z, Kovacević J, van Linn M, Milić M, Rallapalli S, Timić T, Sieghart W, Cook JM, Savić M. Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?. in QSAR & Combinatorial Science. 2013;230(1):113-123.
doi:10.1007/s00213-013-3143-4 .

Joksimović, Srđan, Varagić, Zdravko, Kovacević, Jovana, van Linn, Michael, Milić, Marija, Rallapalli, Sundari, Timić, Tamara, Sieghart, Werner, Cook, James M., Savić, Miroslav, "Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?" in QSAR & Combinatorial Science, 230, no. 1 (2013):113-123,
https://doi.org/10.1007/s00213-013-3143-4 . .

TY  - JOUR
AU  - Timić, Tamara
AU  - Joksimović, Srđan
AU  - Milić, Marija
AU  - Divljaković, Jovana
AU  - Batinić, Bojan
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1957
AB  - Amnesia is one of the most discussed properties of the benzodiazepine class of drugs. The effects of benzodiazepines on human memory are usually anterograde, while changes in retrograde memory functions were seldom reported. Such inconsistent findings have prompted numerous animal studies investigating the influences of these positive modulators of inhibitory neurotransmission on different stages of memory. Among the benzodiazepines, memory effects of midazolam are of special interest due to its many and varied clinical applications. The present Morris water maze study in adult male Wistar rats was performed in three experiments in which midazolam was administered at doses of 0.5, 1 and 2 mg/kg intraperitoneally, before or immediately after each of five daily learning sessions, with two trials in a session, as well as before the probe test. Midazolam impaired acquisition and subsequent retention of spatial learning of the position of the hidden platform even at a pre-training dose of 0.5 mg/kg. This low dose was not associated with impairment of the procedural component of learning, manifested by increased time spent in the periphery of the pool. The lack of midazolam effect on consolidation has not been confounded by the observed below-chance performance of the control group since our additional experiment using diazepam also administered immediately after each of five learning sessions has revealed a similar pattern of results. Finally, midazolam administered before the probe test impaired retrieval of reference memory at all tested doses. Hence, induction of retrograde, besides anterograde amnesia should be kept in mind as a possibility when midazolam is used in clinical settings.
PB  - Elsevier Science BV, Amsterdam
T2  - Behavioural Brain Research
T1  - Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze
VL  - 241
SP  - 198
EP  - 205
DO  - 10.1016/j.bbr.2012.12.014
ER  - 

@article{
author = "Timić, Tamara and Joksimović, Srđan and Milić, Marija and Divljaković, Jovana and Batinić, Bojan and Savić, Miroslav",
year = "2013",
abstract = "Amnesia is one of the most discussed properties of the benzodiazepine class of drugs. The effects of benzodiazepines on human memory are usually anterograde, while changes in retrograde memory functions were seldom reported. Such inconsistent findings have prompted numerous animal studies investigating the influences of these positive modulators of inhibitory neurotransmission on different stages of memory. Among the benzodiazepines, memory effects of midazolam are of special interest due to its many and varied clinical applications. The present Morris water maze study in adult male Wistar rats was performed in three experiments in which midazolam was administered at doses of 0.5, 1 and 2 mg/kg intraperitoneally, before or immediately after each of five daily learning sessions, with two trials in a session, as well as before the probe test. Midazolam impaired acquisition and subsequent retention of spatial learning of the position of the hidden platform even at a pre-training dose of 0.5 mg/kg. This low dose was not associated with impairment of the procedural component of learning, manifested by increased time spent in the periphery of the pool. The lack of midazolam effect on consolidation has not been confounded by the observed below-chance performance of the control group since our additional experiment using diazepam also administered immediately after each of five learning sessions has revealed a similar pattern of results. Finally, midazolam administered before the probe test impaired retrieval of reference memory at all tested doses. Hence, induction of retrograde, besides anterograde amnesia should be kept in mind as a possibility when midazolam is used in clinical settings.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Behavioural Brain Research",
title = "Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze",
volume = "241",
pages = "198-205",
doi = "10.1016/j.bbr.2012.12.014"
}

Timić, T., Joksimović, S., Milić, M., Divljaković, J., Batinić, B.,& Savić, M.. (2013). Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze. in Behavioural Brain Research
Elsevier Science BV, Amsterdam., 241, 198-205.
https://doi.org/10.1016/j.bbr.2012.12.014

Timić T, Joksimović S, Milić M, Divljaković J, Batinić B, Savić M. Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze. in Behavioural Brain Research. 2013;241:198-205.
doi:10.1016/j.bbr.2012.12.014 .

Timić, Tamara, Joksimović, Srđan, Milić, Marija, Divljaković, Jovana, Batinić, Bojan, Savić, Miroslav, "Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze" in Behavioural Brain Research, 241 (2013):198-205,
https://doi.org/10.1016/j.bbr.2012.12.014 . .

TY  - CONF
AU  - Milinković, Marija M.
AU  - Timić, Tamara
AU  - Divljaković, Jovana
AU  - Joksimović, Srđan
AU  - Rallapalli, Sundari
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1660
AB  - Objective : The impairing effects of diazepam in Morris water maze
(MWM) could be partially antagonized with co-administration of an
a5 subunit selective antagonist XLi093 (Savic ́ et al., 2009). In order
to further assess the role of the a5GABAA receptors population
in mediating amnesic effects in rats, the present study examined
effects of an a5GABAA selective agonist XLi356 on the MWM
performance.
Methods : Male Wistar rats were given vehicle or 5, 10 and 20 mg/
kg of XLI356 intraperitoneally 20 minutes before the testing. A single-
day water maze task had three swimming blocks, each consisting of
4 trials, lasting a maximum time of 60 s each. Afterwards, a probe trial
was given and a number of standard parameters was calculated.
Additionally, rats were tested in spontaneous locomotor activity
(SLA) and elevated plus maze (EPM) tests, where the sedative and
anxiolytic effects were assessed.
Results : Results were analyzed using one-way ANOVA with post
hoc Student-Newman-Keuls test where applicable. XLi356 signifi-
cantly increased latency to platform (F(3,444)=3.1287, p=0.026) ; post
hoc test revealed that the dose of 20 mg/kg was significantly different
from vehicle. The same dose of XLi356 significantly increased cumu-
lative distance from the platform zone (p=0.028) and the time spent
in the periphery ring (p=0.009), while the path efficiency was on the
control level. On the other hand, XLi356 did not show behavioral
activity in SLA and EPM tests at either of three doses tested.
Conclusion : The present results suggest that ligands with ap-
preciable agonist activity at GABAA receptors containing a5 subunits
may impair memory acquisition in Morris water maze task, without
discernible effects on general behavior. Thus the activity of the ben-
zodiazepine type drugs at a5GABAA receptors should be decreased if
the amnesic effects are to avoid.
PB  - Oxford Univ Press, Oxford
C3  - International Journal of Neuropsychopharmacology
T1  - The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze
VL  - 15
IS  - Supplement 1
SP  - 231
EP  - 231
DO  - 10.1017/S1461145712000508
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1660
ER  - 

@conference{
author = "Milinković, Marija M. and Timić, Tamara and Divljaković, Jovana and Joksimović, Srđan and Rallapalli, Sundari and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Objective : The impairing effects of diazepam in Morris water maze
(MWM) could be partially antagonized with co-administration of an
a5 subunit selective antagonist XLi093 (Savic ́ et al., 2009). In order
to further assess the role of the a5GABAA receptors population
in mediating amnesic effects in rats, the present study examined
effects of an a5GABAA selective agonist XLi356 on the MWM
performance.
Methods : Male Wistar rats were given vehicle or 5, 10 and 20 mg/
kg of XLI356 intraperitoneally 20 minutes before the testing. A single-
day water maze task had three swimming blocks, each consisting of
4 trials, lasting a maximum time of 60 s each. Afterwards, a probe trial
was given and a number of standard parameters was calculated.
Additionally, rats were tested in spontaneous locomotor activity
(SLA) and elevated plus maze (EPM) tests, where the sedative and
anxiolytic effects were assessed.
Results : Results were analyzed using one-way ANOVA with post
hoc Student-Newman-Keuls test where applicable. XLi356 signifi-
cantly increased latency to platform (F(3,444)=3.1287, p=0.026) ; post
hoc test revealed that the dose of 20 mg/kg was significantly different
from vehicle. The same dose of XLi356 significantly increased cumu-
lative distance from the platform zone (p=0.028) and the time spent
in the periphery ring (p=0.009), while the path efficiency was on the
control level. On the other hand, XLi356 did not show behavioral
activity in SLA and EPM tests at either of three doses tested.
Conclusion : The present results suggest that ligands with ap-
preciable agonist activity at GABAA receptors containing a5 subunits
may impair memory acquisition in Morris water maze task, without
discernible effects on general behavior. Thus the activity of the ben-
zodiazepine type drugs at a5GABAA receptors should be decreased if
the amnesic effects are to avoid.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Journal of Neuropsychopharmacology",
title = "The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze",
volume = "15",
number = "Supplement 1",
pages = "231-231",
doi = "10.1017/S1461145712000508",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1660"
}

Milinković, M. M., Timić, T., Divljaković, J., Joksimović, S., Rallapalli, S., Cook, J. M.,& Savić, M.. (2012). The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze. in International Journal of Neuropsychopharmacology
Oxford Univ Press, Oxford., 15(Supplement 1), 231-231.
https://doi.org/10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1660

Milinković MM, Timić T, Divljaković J, Joksimović S, Rallapalli S, Cook JM, Savić M. The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze. in International Journal of Neuropsychopharmacology. 2012;15(Supplement 1):231-231.
doi:10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1660 .

Milinković, Marija M., Timić, Tamara, Divljaković, Jovana, Joksimović, Srđan, Rallapalli, Sundari, Cook, James M., Savić, Miroslav, "The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze" in International Journal of Neuropsychopharmacology, 15, no. Supplement 1 (2012):231-231,
https://doi.org/10.1017/S1461145712000508 .,
https://hdl.handle.net/21.15107/rcub_farfar_1660 .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Timić, Tamara
AU  - Radulović, Tamara
AU  - Rallapalli, Sundari
AU  - Milinković, Marija M.
AU  - Divljaković, Jovana
AU  - Batinić, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1673
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze
VL  - 22
IS  - Supplement 2
SP  - S190
EP  - S191
DO  - 10.1016/S0924-977X(12)70274-2
ER  - 

@conference{
author = "Joksimović, Srđan and Timić, Tamara and Radulović, Tamara and Rallapalli, Sundari and Milinković, Marija M. and Divljaković, Jovana and Batinić, Bojan and Cook, James M. and Savić, Miroslav",
year = "2012",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze",
volume = "22",
number = "Supplement 2",
pages = "S190-S191",
doi = "10.1016/S0924-977X(12)70274-2"
}

Joksimović, S., Timić, T., Radulović, T., Rallapalli, S., Milinković, M. M., Divljaković, J., Batinić, B., Cook, J. M.,& Savić, M.. (2012). Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 22(Supplement 2), S190-S191.
https://doi.org/10.1016/S0924-977X(12)70274-2

Joksimović S, Timić T, Radulović T, Rallapalli S, Milinković MM, Divljaković J, Batinić B, Cook JM, Savić M. Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze. in European Neuropsychopharmacology. 2012;22(Supplement 2):S190-S191.
doi:10.1016/S0924-977X(12)70274-2 .

Joksimović, Srđan, Timić, Tamara, Radulović, Tamara, Rallapalli, Sundari, Milinković, Marija M., Divljaković, Jovana, Batinić, Bojan, Cook, James M., Savić, Miroslav, "Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze" in European Neuropsychopharmacology, 22, no. Supplement 2 (2012):S190-S191,
https://doi.org/10.1016/S0924-977X(12)70274-2 . .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Huang, Shengming
AU  - Ramerstorfer, Joachim
AU  - Milinković, Marija M.
AU  - Divljaković, Jovana
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Savić, Miroslav
AU  - Cook, James M.
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1350
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile
VL  - 20
IS  - Supplement 3
SP  - S260
EP  - S260
DO  - 10.1016/S0924-977X(10)70331-X
ER  - 

@conference{
author = "Joksimović, Srđan and Huang, Shengming and Ramerstorfer, Joachim and Milinković, Marija M. and Divljaković, Jovana and Roth, Brian L. and Sieghart, Werner and Savić, Miroslav and Cook, James M.",
year = "2010",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile",
volume = "20",
number = "Supplement 3",
pages = "S260-S260",
doi = "10.1016/S0924-977X(10)70331-X"
}

Joksimović, S., Huang, S., Ramerstorfer, J., Milinković, M. M., Divljaković, J., Roth, B. L., Sieghart, W., Savić, M.,& Cook, J. M.. (2010). SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 20(Supplement 3), S260-S260.
https://doi.org/10.1016/S0924-977X(10)70331-X

Joksimović S, Huang S, Ramerstorfer J, Milinković MM, Divljaković J, Roth BL, Sieghart W, Savić M, Cook JM. SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile. in European Neuropsychopharmacology. 2010;20(Supplement 3):S260-S260.
doi:10.1016/S0924-977X(10)70331-X .

Joksimović, Srđan, Huang, Shengming, Ramerstorfer, Joachim, Milinković, Marija M., Divljaković, Jovana, Roth, Brian L., Sieghart, Werner, Savić, Miroslav, Cook, James M., "SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile" in European Neuropsychopharmacology, 20, no. Supplement 3 (2010):S260-S260,
https://doi.org/10.1016/S0924-977X(10)70331-X . .

TY  - CONF
AU  - Milinković, Marija M.
AU  - Samardžić, Janko
AU  - Divljaković, Jovana
AU  - Joksimović, Srđan
AU  - Timić, Tamara
AU  - Savić, Miroslav
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1347
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Midazolam impairs acquisition but not consolidation in water maze paradigm
VL  - 20
IS  - Supplement 3
SP  - S259
EP  - S260
DO  - 10.1016/S0924-977X(10)70330-8
ER  - 

@conference{
author = "Milinković, Marija M. and Samardžić, Janko and Divljaković, Jovana and Joksimović, Srđan and Timić, Tamara and Savić, Miroslav",
year = "2010",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Midazolam impairs acquisition but not consolidation in water maze paradigm",
volume = "20",
number = "Supplement 3",
pages = "S259-S260",
doi = "10.1016/S0924-977X(10)70330-8"
}

Milinković, M. M., Samardžić, J., Divljaković, J., Joksimović, S., Timić, T.,& Savić, M.. (2010). Midazolam impairs acquisition but not consolidation in water maze paradigm. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 20(Supplement 3), S259-S260.
https://doi.org/10.1016/S0924-977X(10)70330-8

Milinković MM, Samardžić J, Divljaković J, Joksimović S, Timić T, Savić M. Midazolam impairs acquisition but not consolidation in water maze paradigm. in European Neuropsychopharmacology. 2010;20(Supplement 3):S259-S260.
doi:10.1016/S0924-977X(10)70330-8 .

Milinković, Marija M., Samardžić, Janko, Divljaković, Jovana, Joksimović, Srđan, Timić, Tamara, Savić, Miroslav, "Midazolam impairs acquisition but not consolidation in water maze paradigm" in European Neuropsychopharmacology, 20, no. Supplement 3 (2010):S259-S260,
https://doi.org/10.1016/S0924-977X(10)70330-8 . .

TY  - JOUR
AU  - Savić, Miroslav
AU  - Majumder, Samarpan
AU  - Huang, Shengming
AU  - Edwankar, Rahul V.
AU  - Furtmueller, Roman
AU  - Joksimović, Srđan
AU  - Clayton, Terry
AU  - Ramerstorfer, Joachim
AU  - Milinković, Marija M.
AU  - Roth, Bryan L.
AU  - Sieghart, Werner
AU  - Cook, James M.
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1380
AB  - Over the last years, genetic studies have greatly improved Our knowledge on the receptor subtypes mediating various pharmacological effects of positive allosteric modulators at GABA(A) receptors. This stimulated the development of new benzodiazepine (BZ)-like ligands, especially those inactive/low-active at GABA(A) receptors containing the alpha(1) subunit, with the aim of generating more selective drugs. Hereby, the affinity and efficacy of four recently synthesized BZ site ligands: SH-053-2'N, SH-053-S-CH3-2'F, SH-053-R-CH3-2'F and JY-XHe-053 were assessed. They were also studied in behavioral tests of spontaneous locomotor activity, elevated plus maze, and water maze in rats, which are considered predictive of. respectively, the sedative, anxiolytic, and amnesic influence of BZs. The novel ligands had moderately low to low affinity and mild to partial agonistic efficacy at GABA(A) receptors containing the a, subunit, with variable, but more pronounced efficacy at other BZ-sensitive binding sites. While presumably alpha(1) receptor-mediated sedative effects of GABA(A) modulation were not fully eliminated with any of the ligands tested, only SH-053-2'N and SH-053-S-CH3-2'F, both dosed at 30 mg/kg, exerted anxiolytic effects. The lack of clear anxiolytic-like activity of JY-XHe-053, despite its efficacy at alpha(2)- and alpha(3)-GABA(A) receptors, may have been partly connected with its preferential affinity at alpha(5)-GABA(A) receptors coupled with weak agonist activity at alpha(1)-containing subtypes. The memory impairment in water-maze experiments, generally reported with BZ site agonists, was completely circumvented with all four ligands. The results suggest that a substantial amount of activity at a I GABA(A) receptors is needed for affecting spatial learning and memory impairments, while much weaker activity at alpha(1) and alpha(5)-GABA(A) receptors is sufficient for eliciting sedation.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Progress in Nutrition
T1  - Novel positive allosteric modulators of GABAA receptors: Do subtle differences in activity at alpha 1 plus alpha 5 versus alpha 2 plus alpha 3 subunits account for dissimilarities in behavioral effects in rats?
VL  - 34
IS  - 2
SP  - 376
EP  - 386
DO  - 10.1016/j.pnpbp.2010.01.004
ER  - 

@article{
author = "Savić, Miroslav and Majumder, Samarpan and Huang, Shengming and Edwankar, Rahul V. and Furtmueller, Roman and Joksimović, Srđan and Clayton, Terry and Ramerstorfer, Joachim and Milinković, Marija M. and Roth, Bryan L. and Sieghart, Werner and Cook, James M.",
year = "2010",
abstract = "Over the last years, genetic studies have greatly improved Our knowledge on the receptor subtypes mediating various pharmacological effects of positive allosteric modulators at GABA(A) receptors. This stimulated the development of new benzodiazepine (BZ)-like ligands, especially those inactive/low-active at GABA(A) receptors containing the alpha(1) subunit, with the aim of generating more selective drugs. Hereby, the affinity and efficacy of four recently synthesized BZ site ligands: SH-053-2'N, SH-053-S-CH3-2'F, SH-053-R-CH3-2'F and JY-XHe-053 were assessed. They were also studied in behavioral tests of spontaneous locomotor activity, elevated plus maze, and water maze in rats, which are considered predictive of. respectively, the sedative, anxiolytic, and amnesic influence of BZs. The novel ligands had moderately low to low affinity and mild to partial agonistic efficacy at GABA(A) receptors containing the a, subunit, with variable, but more pronounced efficacy at other BZ-sensitive binding sites. While presumably alpha(1) receptor-mediated sedative effects of GABA(A) modulation were not fully eliminated with any of the ligands tested, only SH-053-2'N and SH-053-S-CH3-2'F, both dosed at 30 mg/kg, exerted anxiolytic effects. The lack of clear anxiolytic-like activity of JY-XHe-053, despite its efficacy at alpha(2)- and alpha(3)-GABA(A) receptors, may have been partly connected with its preferential affinity at alpha(5)-GABA(A) receptors coupled with weak agonist activity at alpha(1)-containing subtypes. The memory impairment in water-maze experiments, generally reported with BZ site agonists, was completely circumvented with all four ligands. The results suggest that a substantial amount of activity at a I GABA(A) receptors is needed for affecting spatial learning and memory impairments, while much weaker activity at alpha(1) and alpha(5)-GABA(A) receptors is sufficient for eliciting sedation.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Progress in Nutrition",
title = "Novel positive allosteric modulators of GABAA receptors: Do subtle differences in activity at alpha 1 plus alpha 5 versus alpha 2 plus alpha 3 subunits account for dissimilarities in behavioral effects in rats?",
volume = "34",
number = "2",
pages = "376-386",
doi = "10.1016/j.pnpbp.2010.01.004"
}

Savić, M., Majumder, S., Huang, S., Edwankar, R. V., Furtmueller, R., Joksimović, S., Clayton, T., Ramerstorfer, J., Milinković, M. M., Roth, B. L., Sieghart, W.,& Cook, J. M.. (2010). Novel positive allosteric modulators of GABAA receptors: Do subtle differences in activity at alpha 1 plus alpha 5 versus alpha 2 plus alpha 3 subunits account for dissimilarities in behavioral effects in rats?. in Progress in Nutrition
Pergamon-Elsevier Science Ltd, Oxford., 34(2), 376-386.
https://doi.org/10.1016/j.pnpbp.2010.01.004

Savić M, Majumder S, Huang S, Edwankar RV, Furtmueller R, Joksimović S, Clayton T, Ramerstorfer J, Milinković MM, Roth BL, Sieghart W, Cook JM. Novel positive allosteric modulators of GABAA receptors: Do subtle differences in activity at alpha 1 plus alpha 5 versus alpha 2 plus alpha 3 subunits account for dissimilarities in behavioral effects in rats?. in Progress in Nutrition. 2010;34(2):376-386.
doi:10.1016/j.pnpbp.2010.01.004 .

Savić, Miroslav, Majumder, Samarpan, Huang, Shengming, Edwankar, Rahul V., Furtmueller, Roman, Joksimović, Srđan, Clayton, Terry, Ramerstorfer, Joachim, Milinković, Marija M., Roth, Bryan L., Sieghart, Werner, Cook, James M., "Novel positive allosteric modulators of GABAA receptors: Do subtle differences in activity at alpha 1 plus alpha 5 versus alpha 2 plus alpha 3 subunits account for dissimilarities in behavioral effects in rats?" in Progress in Nutrition, 34, no. 2 (2010):376-386,
https://doi.org/10.1016/j.pnpbp.2010.01.004 . .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Savić, Miroslav
AU  - Milinković, Marija M.
AU  - van Linn, Michael
AU  - Ramerstorfer, Joachim
AU  - Majumder, Samarpan
AU  - Yin, Wenyuan
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Cook, James M.
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1172
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?
VL  - 19
IS  - Supplement 3
SP  - S297
EP  - S297
DO  - 10.1016/S0924-977X(09)70440-7
ER  - 

@conference{
author = "Joksimović, Srđan and Savić, Miroslav and Milinković, Marija M. and van Linn, Michael and Ramerstorfer, Joachim and Majumder, Samarpan and Yin, Wenyuan and Roth, Brian L. and Sieghart, Werner and Cook, James M.",
year = "2009",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?",
volume = "19",
number = "Supplement 3",
pages = "S297-S297",
doi = "10.1016/S0924-977X(09)70440-7"
}

Joksimović, S., Savić, M., Milinković, M. M., van Linn, M., Ramerstorfer, J., Majumder, S., Yin, W., Roth, B. L., Sieghart, W.,& Cook, J. M.. (2009). WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 19(Supplement 3), S297-S297.
https://doi.org/10.1016/S0924-977X(09)70440-7

Joksimović S, Savić M, Milinković MM, van Linn M, Ramerstorfer J, Majumder S, Yin W, Roth BL, Sieghart W, Cook JM. WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?. in European Neuropsychopharmacology. 2009;19(Supplement 3):S297-S297.
doi:10.1016/S0924-977X(09)70440-7 .

Joksimović, Srđan, Savić, Miroslav, Milinković, Marija M., van Linn, Michael, Ramerstorfer, Joachim, Majumder, Samarpan, Yin, Wenyuan, Roth, Brian L., Sieghart, Werner, Cook, James M., "WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?" in European Neuropsychopharmacology, 19, no. Supplement 3 (2009):S297-S297,
https://doi.org/10.1016/S0924-977X(09)70440-7 . .

TY  - JOUR
AU  - Savić, Miroslav
AU  - Milinković, Marija M.
AU  - Rallapalli, Sundari
AU  - Clayton, Terry
AU  - Joksimović, Srđan
AU  - van Linn, Michael
AU  - Cook, James M.
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1176
AB  - The clinical use of benzodiazepines (BZs) is hampered by sedation and cognitive deterioration. Although genetic and pharmacological studies suggest that alpha(1)- and alpha(5)-containing GABA(A) receptors mediate and/or modulate these effects, their molecular substrate is not fully elucidated. By the use of two selective ligands: the alpha(1)-subunit affinity-selective antagonist beta-CCt, and the alpha(5)-subunit affinity- and efficacy-selective antagonist XLi093, we examined the mechanisms of behavioural effects of diazepam in the tests of spontaneous locomotor activity and water-maze acquisition and recall, the two paradigms indicative of sedative- and cognition-impairing effects of BZs, respectively. The locomotor-activity decreasing propensity of diazepam (significant at 1.5 and 5 mg/kg) was antagonized by beta-CCt (5 and 15 mg/kg), while it tended to be potentiated by XLi093 in doses of 10 mg/kg, and especially 20 mg/kg. Diazepam decreased acquisition and recall in the water maze, with a minimum effective dose of 1.5 mg/kg. Both antagonists reversed the thigmotaxis induced by 2 mg/kg diazepam throughout the test, suggesting that both GABA(A) receptor subtypes participate in BZ effects on the procedural component of the task. Diazepam-induced impairment in the declarative component of the task, as assessed by path efficiency, the latency and distance before finding the platform across acquisition trials, and also by the spatial parameters in the probe trial, was partially prevented by both, 15 mg/kg beta-CCt and 10 mg/kg XLi093. Combining a BZ with beta-CCt results in the near to control level of performance of a cognitive task, without sedation, and may be worth testing on human subjects.
PB  - Oxford Univ Press, Oxford
T2  - International Journal of Neuropsychopharmacology
T1  - The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats
VL  - 12
IS  - 9
SP  - 1179
EP  - 1193
DO  - 10.1017/S1461145709000108
ER  - 

@article{
author = "Savić, Miroslav and Milinković, Marija M. and Rallapalli, Sundari and Clayton, Terry and Joksimović, Srđan and van Linn, Michael and Cook, James M.",
year = "2009",
abstract = "The clinical use of benzodiazepines (BZs) is hampered by sedation and cognitive deterioration. Although genetic and pharmacological studies suggest that alpha(1)- and alpha(5)-containing GABA(A) receptors mediate and/or modulate these effects, their molecular substrate is not fully elucidated. By the use of two selective ligands: the alpha(1)-subunit affinity-selective antagonist beta-CCt, and the alpha(5)-subunit affinity- and efficacy-selective antagonist XLi093, we examined the mechanisms of behavioural effects of diazepam in the tests of spontaneous locomotor activity and water-maze acquisition and recall, the two paradigms indicative of sedative- and cognition-impairing effects of BZs, respectively. The locomotor-activity decreasing propensity of diazepam (significant at 1.5 and 5 mg/kg) was antagonized by beta-CCt (5 and 15 mg/kg), while it tended to be potentiated by XLi093 in doses of 10 mg/kg, and especially 20 mg/kg. Diazepam decreased acquisition and recall in the water maze, with a minimum effective dose of 1.5 mg/kg. Both antagonists reversed the thigmotaxis induced by 2 mg/kg diazepam throughout the test, suggesting that both GABA(A) receptor subtypes participate in BZ effects on the procedural component of the task. Diazepam-induced impairment in the declarative component of the task, as assessed by path efficiency, the latency and distance before finding the platform across acquisition trials, and also by the spatial parameters in the probe trial, was partially prevented by both, 15 mg/kg beta-CCt and 10 mg/kg XLi093. Combining a BZ with beta-CCt results in the near to control level of performance of a cognitive task, without sedation, and may be worth testing on human subjects.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Journal of Neuropsychopharmacology",
title = "The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats",
volume = "12",
number = "9",
pages = "1179-1193",
doi = "10.1017/S1461145709000108"
}

Savić, M., Milinković, M. M., Rallapalli, S., Clayton, T., Joksimović, S., van Linn, M.,& Cook, J. M.. (2009). The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats. in International Journal of Neuropsychopharmacology
Oxford Univ Press, Oxford., 12(9), 1179-1193.
https://doi.org/10.1017/S1461145709000108

Savić M, Milinković MM, Rallapalli S, Clayton T, Joksimović S, van Linn M, Cook JM. The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats. in International Journal of Neuropsychopharmacology. 2009;12(9):1179-1193.
doi:10.1017/S1461145709000108 .

Savić, Miroslav, Milinković, Marija M., Rallapalli, Sundari, Clayton, Terry, Joksimović, Srđan, van Linn, Michael, Cook, James M., "The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats" in International Journal of Neuropsychopharmacology, 12, no. 9 (2009):1179-1193,
https://doi.org/10.1017/S1461145709000108 . .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Savić, Miroslav
AU  - Clayton, Terry
AU  - Huang, Shengming
AU  - Ara, S.
AU  - van Linn, Michael
AU  - Milinković, Marija M.
AU  - Bokonjić, Dubravko
AU  - Sieghart, Werner
AU  - Cook, James M.
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1079
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze
VL  - 18
IS  - Supplement 4
SP  - S282
EP  - S282
DO  - 10.1016/S0924-977X(08)70372-9
ER  - 

@conference{
author = "Joksimović, Srđan and Savić, Miroslav and Clayton, Terry and Huang, Shengming and Ara, S. and van Linn, Michael and Milinković, Marija M. and Bokonjić, Dubravko and Sieghart, Werner and Cook, James M.",
year = "2008",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze",
volume = "18",
number = "Supplement 4",
pages = "S282-S282",
doi = "10.1016/S0924-977X(08)70372-9"
}

Joksimović, S., Savić, M., Clayton, T., Huang, S., Ara, S., van Linn, M., Milinković, M. M., Bokonjić, D., Sieghart, W.,& Cook, J. M.. (2008). Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 18(Supplement 4), S282-S282.
https://doi.org/10.1016/S0924-977X(08)70372-9

Joksimović S, Savić M, Clayton T, Huang S, Ara S, van Linn M, Milinković MM, Bokonjić D, Sieghart W, Cook JM. Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze. in European Neuropsychopharmacology. 2008;18(Supplement 4):S282-S282.
doi:10.1016/S0924-977X(08)70372-9 .

Joksimović, Srđan, Savić, Miroslav, Clayton, Terry, Huang, Shengming, Ara, S., van Linn, Michael, Milinković, Marija M., Bokonjić, Dubravko, Sieghart, Werner, Cook, James M., "Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze" in European Neuropsychopharmacology, 18, no. Supplement 4 (2008):S282-S282,
https://doi.org/10.1016/S0924-977X(08)70372-9 . .

TY  - CONF
AU  - Samardžić, Janko
AU  - Savić, Miroslav
AU  - Clayton, Terry
AU  - Rallapalli, Sundari
AU  - Obradović, Dragan I.
AU  - Joksimović, Srđan
AU  - Sieghart, Werner
AU  - Cook, James M.
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1025
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Effects of a novel inverse agonist selective for alpha5 GABAA receptors on spatial memory: comparison with the standard non-selective inverse agonist DMCM
VL  - 18
IS  - Supplement 4
SP  - S285
EP  - S285
DO  - 10.1016/S0924-977X(08)70377-8
ER  - 

@conference{
author = "Samardžić, Janko and Savić, Miroslav and Clayton, Terry and Rallapalli, Sundari and Obradović, Dragan I. and Joksimović, Srđan and Sieghart, Werner and Cook, James M.",
year = "2008",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Effects of a novel inverse agonist selective for alpha5 GABAA receptors on spatial memory: comparison with the standard non-selective inverse agonist DMCM",
volume = "18",
number = "Supplement 4",
pages = "S285-S285",
doi = "10.1016/S0924-977X(08)70377-8"
}

Samardžić, J., Savić, M., Clayton, T., Rallapalli, S., Obradović, D. I., Joksimović, S., Sieghart, W.,& Cook, J. M.. (2008). Effects of a novel inverse agonist selective for alpha5 GABAA receptors on spatial memory: comparison with the standard non-selective inverse agonist DMCM. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 18(Supplement 4), S285-S285.
https://doi.org/10.1016/S0924-977X(08)70377-8

Samardžić J, Savić M, Clayton T, Rallapalli S, Obradović DI, Joksimović S, Sieghart W, Cook JM. Effects of a novel inverse agonist selective for alpha5 GABAA receptors on spatial memory: comparison with the standard non-selective inverse agonist DMCM. in European Neuropsychopharmacology. 2008;18(Supplement 4):S285-S285.
doi:10.1016/S0924-977X(08)70377-8 .

Samardžić, Janko, Savić, Miroslav, Clayton, Terry, Rallapalli, Sundari, Obradović, Dragan I., Joksimović, Srđan, Sieghart, Werner, Cook, James M., "Effects of a novel inverse agonist selective for alpha5 GABAA receptors on spatial memory: comparison with the standard non-selective inverse agonist DMCM" in European Neuropsychopharmacology, 18, no. Supplement 4 (2008):S285-S285,
https://doi.org/10.1016/S0924-977X(08)70377-8 . .