TY  - JOUR
AU  - Paranos, Sonja
AU  - Tomić, Maja
AU  - Micov, Ana
AU  - Stepanović-Petrović, Radica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1986
AB  - Recent studies have shown that topiramate, a structurally novel anticonvulsant, exerts antinociceptive activity in animal models of neuropathic, acute somatic, and visceral pain. This study was aimed to examine: (i) the effects of systemically and locally peripherally administered topiramate in the rat inflammatory pain model and (ii) the potential role and site(s) of gamma-aminobutyric acid (GABA), opioid, and adrenergic receptors in topiramate's antihyperalgesia. Rats received intraplantar (i.pl.) injections of the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of systemic and local peripheral topiramate on carrageenan-induced hyperalgesia and (ii) the effects of systemic and local peripheral bicuculline (selective GABAA receptor antagonist), naloxone (nonselective opioid receptor antagonist), and yohimbine (selective 2-adrenergic receptor antagonist) on topiramate-induced antihyperalgesia. Systemic topiramate (40160mg/kg; p.o.) produced a significant dose-dependent reduction in the paw inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of systemic topiramate was significantly decreased by systemic bicuculline (0.51mg/kg; i.p.), naloxone (25mg/kg; i.p.), and yohimbine (13mg/kg; i.p.). Local peripheral topiramate (0.030.34mg/paw; i.pl.) also produced significant dose-dependent antihyperalgesia, which was significantly depressed by local peripheral yohimbine (0.050.2mg/paw; i.pl.) but not by local peripheral bicuculline (0.15mg/paw; i.pl.) or naloxone (0.1mg/paw; i.pl.). The results suggest that topiramate produces systemic and local peripheral antihyperalgesia in an inflammatory pain model, which is, at least partially, mediated by central GABAA and opioid receptors and by peripheral and most probably central 2-adrenergic receptors. These findings contribute to better understanding of topiramate's action in pain states involving inflammation.
PB  - Wiley-Blackwell, Hoboken
T2  - Fundamental & Clinical Pharmacology
T1  - The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia
VL  - 27
IS  - 3
SP  - 319
EP  - 328
DO  - 10.1111/j.1472-8206.2011.01018.x
ER  - 

@article{
author = "Paranos, Sonja and Tomić, Maja and Micov, Ana and Stepanović-Petrović, Radica",
year = "2013",
abstract = "Recent studies have shown that topiramate, a structurally novel anticonvulsant, exerts antinociceptive activity in animal models of neuropathic, acute somatic, and visceral pain. This study was aimed to examine: (i) the effects of systemically and locally peripherally administered topiramate in the rat inflammatory pain model and (ii) the potential role and site(s) of gamma-aminobutyric acid (GABA), opioid, and adrenergic receptors in topiramate's antihyperalgesia. Rats received intraplantar (i.pl.) injections of the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of systemic and local peripheral topiramate on carrageenan-induced hyperalgesia and (ii) the effects of systemic and local peripheral bicuculline (selective GABAA receptor antagonist), naloxone (nonselective opioid receptor antagonist), and yohimbine (selective 2-adrenergic receptor antagonist) on topiramate-induced antihyperalgesia. Systemic topiramate (40160mg/kg; p.o.) produced a significant dose-dependent reduction in the paw inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of systemic topiramate was significantly decreased by systemic bicuculline (0.51mg/kg; i.p.), naloxone (25mg/kg; i.p.), and yohimbine (13mg/kg; i.p.). Local peripheral topiramate (0.030.34mg/paw; i.pl.) also produced significant dose-dependent antihyperalgesia, which was significantly depressed by local peripheral yohimbine (0.050.2mg/paw; i.pl.) but not by local peripheral bicuculline (0.15mg/paw; i.pl.) or naloxone (0.1mg/paw; i.pl.). The results suggest that topiramate produces systemic and local peripheral antihyperalgesia in an inflammatory pain model, which is, at least partially, mediated by central GABAA and opioid receptors and by peripheral and most probably central 2-adrenergic receptors. These findings contribute to better understanding of topiramate's action in pain states involving inflammation.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Fundamental & Clinical Pharmacology",
title = "The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia",
volume = "27",
number = "3",
pages = "319-328",
doi = "10.1111/j.1472-8206.2011.01018.x"
}

Paranos, S., Tomić, M., Micov, A.,& Stepanović-Petrović, R.. (2013). The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia. in Fundamental & Clinical Pharmacology
Wiley-Blackwell, Hoboken., 27(3), 319-328.
https://doi.org/10.1111/j.1472-8206.2011.01018.x

Paranos S, Tomić M, Micov A, Stepanović-Petrović R. The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia. in Fundamental & Clinical Pharmacology. 2013;27(3):319-328.
doi:10.1111/j.1472-8206.2011.01018.x .

Paranos, Sonja, Tomić, Maja, Micov, Ana, Stepanović-Petrović, Radica, "The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia" in Fundamental & Clinical Pharmacology, 27, no. 3 (2013):319-328,
https://doi.org/10.1111/j.1472-8206.2011.01018.x . .

TY  - JOUR
AU  - Stepanović-Petrović, Radica
AU  - Tomić, Maja
AU  - Vučković, Sonja M.
AU  - Paranos, Sonja
AU  - Ugrešić, Nenad
AU  - Prostran, Milica
AU  - Milovanović, Slobocian
AU  - Bošković, Bogdan
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1067
AB  - BACKGROUND: There is evidence supporting the antinociceptive effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in various models of neuropathic pain as well as inflammatory somatic pain. Data are lacking on the antinociceptive potential of these drugs against visceral pain. In this study, we examined and compared the effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in the writhing test as a visceral pain model in the mouse. In addition, the influence of these anticonvulsants on motor performance was examined to compare the tolerability of these anticonvulsants when used against acute visceral pain. METHODS: The antinociceptive effects of these anticonvulsants were examined in the acetic acid writhing test in mice. The side effect propensity of these drugs was examined using the rotarod test. RESULTS: Carbamazepine (25-60 mg/kg; p.o.), oxcarbazepine (10-40 mg/kg; p.o.), gabapentin (10-70 mg/kg; p.o.), and topiramate (5-30 mg/kg; p.o.) caused a significant dose-dependent reduction the number of writhes in the writhing test. In the rotarod test, carbamazepine (60-140 mg/kg; p.o.) and oxcarbazepine (120-450 mg/kg; p.o.) significantly reduced the time spent on the rotarod in a dose- and time-dependent manner. Gabapentin (1000-2000 mg/kg; p.o.) and topiramate (400-1500 mg/kg; p.o.) did not produce significant impairment of motor performance at the highest doses used. The therapeutic index (motor impairing dose TD50)/writhing ED50) values were topiramate (>148.5) > gabapentin (>60.2) > oxcarbazepine (15.2) > carbamazepine (2.3). CONCLUSIONS: These results indicate that oxcarbazepine, gabapentin, and topiramate are effective in the writhing model in mice, in a dose range, which is not related to motor impairment; topiramate is the most potent and the most tolerable drug.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - The antinociceptive effects of anticonvulsants in a mouse visceral pain model
VL  - 106
IS  - 6
SP  - 1897
EP  - 1903
DO  - 10.1213/ane.0b013618172b993
ER  - 

@article{
author = "Stepanović-Petrović, Radica and Tomić, Maja and Vučković, Sonja M. and Paranos, Sonja and Ugrešić, Nenad and Prostran, Milica and Milovanović, Slobocian and Bošković, Bogdan",
year = "2008",
abstract = "BACKGROUND: There is evidence supporting the antinociceptive effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in various models of neuropathic pain as well as inflammatory somatic pain. Data are lacking on the antinociceptive potential of these drugs against visceral pain. In this study, we examined and compared the effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in the writhing test as a visceral pain model in the mouse. In addition, the influence of these anticonvulsants on motor performance was examined to compare the tolerability of these anticonvulsants when used against acute visceral pain. METHODS: The antinociceptive effects of these anticonvulsants were examined in the acetic acid writhing test in mice. The side effect propensity of these drugs was examined using the rotarod test. RESULTS: Carbamazepine (25-60 mg/kg; p.o.), oxcarbazepine (10-40 mg/kg; p.o.), gabapentin (10-70 mg/kg; p.o.), and topiramate (5-30 mg/kg; p.o.) caused a significant dose-dependent reduction the number of writhes in the writhing test. In the rotarod test, carbamazepine (60-140 mg/kg; p.o.) and oxcarbazepine (120-450 mg/kg; p.o.) significantly reduced the time spent on the rotarod in a dose- and time-dependent manner. Gabapentin (1000-2000 mg/kg; p.o.) and topiramate (400-1500 mg/kg; p.o.) did not produce significant impairment of motor performance at the highest doses used. The therapeutic index (motor impairing dose TD50)/writhing ED50) values were topiramate (>148.5) > gabapentin (>60.2) > oxcarbazepine (15.2) > carbamazepine (2.3). CONCLUSIONS: These results indicate that oxcarbazepine, gabapentin, and topiramate are effective in the writhing model in mice, in a dose range, which is not related to motor impairment; topiramate is the most potent and the most tolerable drug.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
title = "The antinociceptive effects of anticonvulsants in a mouse visceral pain model",
volume = "106",
number = "6",
pages = "1897-1903",
doi = "10.1213/ane.0b013618172b993"
}

Stepanović-Petrović, R., Tomić, M., Vučković, S. M., Paranos, S., Ugrešić, N., Prostran, M., Milovanović, S.,& Bošković, B.. (2008). The antinociceptive effects of anticonvulsants in a mouse visceral pain model. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 106(6), 1897-1903.
https://doi.org/10.1213/ane.0b013618172b993

Stepanović-Petrović R, Tomić M, Vučković SM, Paranos S, Ugrešić N, Prostran M, Milovanović S, Bošković B. The antinociceptive effects of anticonvulsants in a mouse visceral pain model. in Anesthesia and Analgesia. 2008;106(6):1897-1903.
doi:10.1213/ane.0b013618172b993 .

Stepanović-Petrović, Radica, Tomić, Maja, Vučković, Sonja M., Paranos, Sonja, Ugrešić, Nenad, Prostran, Milica, Milovanović, Slobocian, Bošković, Bogdan, "The antinociceptive effects of anticonvulsants in a mouse visceral pain model" in Anesthesia and Analgesia, 106, no. 6 (2008):1897-1903,
https://doi.org/10.1213/ane.0b013618172b993 . .

TY  - JOUR
AU  - Tomić, Maja
AU  - Vučković, Sonja M.
AU  - Stepanović-Petrović, Radica
AU  - Ugrešić, Nenad
AU  - Paranos, Sonja
AU  - Prostran, Milica
AU  - Bošković, Bogdan
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/983
AB  - We studied whether peripheral alpha(2)-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha(2)-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)- adrenoceptor antagonist), MK-912 (selective alpha(2C)-adrenoceptor antagonist), and clonidine (alpha(2)-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. METHODS: Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. RESULTS: Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.. pl.), BRL44408 (100 and 200 nmol/paw,-i.pl.),and MK-912 (10and 20 nmol/paw;i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/pav\T,I i.pl.) in a close-dependent mariner. The effects of antagonists were due to local effects since they were not observed after admirdstration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED50 (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. lsobolographic analysis revealed an additive antihyperalgesic effect. CONCLUSIONS: Our results indicate that the peripheral a,A and a,c adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia. (Anesth Analg 2007;105:1474-81)
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain
VL  - 105
IS  - 5
SP  - 1474
EP  - 1481
DO  - 10.1213/01.ane.0000287270.35176.3e
ER  - 

@article{
author = "Tomić, Maja and Vučković, Sonja M. and Stepanović-Petrović, Radica and Ugrešić, Nenad and Paranos, Sonja and Prostran, Milica and Bošković, Bogdan",
year = "2007",
abstract = "We studied whether peripheral alpha(2)-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha(2)-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)- adrenoceptor antagonist), MK-912 (selective alpha(2C)-adrenoceptor antagonist), and clonidine (alpha(2)-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. METHODS: Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. RESULTS: Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.. pl.), BRL44408 (100 and 200 nmol/paw,-i.pl.),and MK-912 (10and 20 nmol/paw;i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/pav\T,I i.pl.) in a close-dependent mariner. The effects of antagonists were due to local effects since they were not observed after admirdstration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED50 (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. lsobolographic analysis revealed an additive antihyperalgesic effect. CONCLUSIONS: Our results indicate that the peripheral a,A and a,c adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia. (Anesth Analg 2007;105:1474-81)",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
title = "The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain",
volume = "105",
number = "5",
pages = "1474-1481",
doi = "10.1213/01.ane.0000287270.35176.3e"
}

Tomić, M., Vučković, S. M., Stepanović-Petrović, R., Ugrešić, N., Paranos, S., Prostran, M.,& Bošković, B.. (2007). The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 105(5), 1474-1481.
https://doi.org/10.1213/01.ane.0000287270.35176.3e

Tomić M, Vučković SM, Stepanović-Petrović R, Ugrešić N, Paranos S, Prostran M, Bošković B. The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain. in Anesthesia and Analgesia. 2007;105(5):1474-1481.
doi:10.1213/01.ane.0000287270.35176.3e .

Tomić, Maja, Vučković, Sonja M., Stepanović-Petrović, Radica, Ugrešić, Nenad, Paranos, Sonja, Prostran, Milica, Bošković, Bogdan, "The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain" in Anesthesia and Analgesia, 105, no. 5 (2007):1474-1481,
https://doi.org/10.1213/01.ane.0000287270.35176.3e . .