TY  - CHAP
AU  - Jokanović, Milan
AU  - Antonijević, Biljana
AU  - Vučinić, Slavica
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1582
PB  - John Wiley and Sons
T2  - Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology
T1  - Epidemiological Studies of Anticholinesterase Pesticide Poisoning in Serbia
SP  - 481
EP  - 494
DO  - 10.1002/9780470640500.ch35
ER  - 

@inbook{
author = "Jokanović, Milan and Antonijević, Biljana and Vučinić, Slavica",
year = "2011",
publisher = "John Wiley and Sons",
journal = "Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology",
booktitle = "Epidemiological Studies of Anticholinesterase Pesticide Poisoning in Serbia",
pages = "481-494",
doi = "10.1002/9780470640500.ch35"
}

Jokanović, M., Antonijević, B.,& Vučinić, S.. (2011). Epidemiological Studies of Anticholinesterase Pesticide Poisoning in Serbia. in Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology
John Wiley and Sons., 481-494.
https://doi.org/10.1002/9780470640500.ch35

Jokanović M, Antonijević B, Vučinić S. Epidemiological Studies of Anticholinesterase Pesticide Poisoning in Serbia. in Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology. 2011;:481-494.
doi:10.1002/9780470640500.ch35 .

Jokanović, Milan, Antonijević, Biljana, Vučinić, Slavica, "Epidemiological Studies of Anticholinesterase Pesticide Poisoning in Serbia" in Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology (2011):481-494,
https://doi.org/10.1002/9780470640500.ch35 . .

TY  - JOUR
AU  - Stepanović-Petrović, Radica
AU  - Savić, Vladimir
AU  - Tomić, Maja
AU  - Tokić-Vujošević, Zorana
AU  - Simić, Milena
AU  - Stepanović, Jelena M.
AU  - Jokanović, Milan
AU  - Micov, Ana
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1337
AB  - Background/Aims: 5-Ketoximeisosorbide-2-mononitrate (50-IS-2-MN) was synthesized and its pharmacological and toxicological characteristics were examined and compared with its parent drug, isosorbide-5-mononitrate (IS-5-MN, CAS 16051-77-7), and its diastereoisomer 2-ketoximeisosorbide-5-mononitrate. Methods: Vasorelaxation was studied on phenylephrine-precontracted rat superior mesenteric artery rings in organ bath procedure. In some rings, the endothelium was mechanically removed. In vitro tolerance was induced by treating the precontracted rings with maximal concentrations of the parent drug and the ketoximes, and after washing out, the procedure was repeated for two times. Furthermore, rats were treated with a single oral dose (1000 mg/kg) of 50-IS-2-MN and 20-IS-5-MN. Results: After a phenylephrine-induced contraction, 50-IS-2-MN (10(-8)-10(-4) mol/l) caused a concentration-dependent relaxation of the rat superior mesenteric artery that was strongly potentiated after the removal of the vascular endothelium. In preparations with or without endothelium, 50-IS-2-MN was a more potent relaxant than either the parent compound or its isomer. The mechanism of the relaxant effect of 50-IS-2-MN involves the activated soluble guanylyl cyclase-cyclic GMP pathway. Hydralazine (10(-5) mol/l), a strong antioxidant, ameliorated tolerance to IS-5-MN, but did not affect the absence of tolerance to either ketoxime. The minimum lethal dose in rat for 50-IS-2-MN and 20-IS-5-MN was greater than 1000 mg/kg. Conclusion: These results suggest that the modification of the configuration at the ester carbon of IS-5-MN contributes to more potent and tolerance-devoid activity on the rat superior mesenteric artery.
PB  - ECV-Editio Cantor Verlag Medizin Naturwissenschaften, Aulendorf
T2  - Arzneimittelforschung - Drug Research
T1  - Comparison of vasorelaxant effect and tolerance profile of a novel isosorbide-5-mononitrate derivative with its stereoisomer and parent drug on rat mesenteric artery
VL  - 60
IS  - 4
SP  - 189
EP  - 197
DO  - 10.1055/s-0031-1296272
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1337
ER  - 

@article{
author = "Stepanović-Petrović, Radica and Savić, Vladimir and Tomić, Maja and Tokić-Vujošević, Zorana and Simić, Milena and Stepanović, Jelena M. and Jokanović, Milan and Micov, Ana",
year = "2010",
abstract = "Background/Aims: 5-Ketoximeisosorbide-2-mononitrate (50-IS-2-MN) was synthesized and its pharmacological and toxicological characteristics were examined and compared with its parent drug, isosorbide-5-mononitrate (IS-5-MN, CAS 16051-77-7), and its diastereoisomer 2-ketoximeisosorbide-5-mononitrate. Methods: Vasorelaxation was studied on phenylephrine-precontracted rat superior mesenteric artery rings in organ bath procedure. In some rings, the endothelium was mechanically removed. In vitro tolerance was induced by treating the precontracted rings with maximal concentrations of the parent drug and the ketoximes, and after washing out, the procedure was repeated for two times. Furthermore, rats were treated with a single oral dose (1000 mg/kg) of 50-IS-2-MN and 20-IS-5-MN. Results: After a phenylephrine-induced contraction, 50-IS-2-MN (10(-8)-10(-4) mol/l) caused a concentration-dependent relaxation of the rat superior mesenteric artery that was strongly potentiated after the removal of the vascular endothelium. In preparations with or without endothelium, 50-IS-2-MN was a more potent relaxant than either the parent compound or its isomer. The mechanism of the relaxant effect of 50-IS-2-MN involves the activated soluble guanylyl cyclase-cyclic GMP pathway. Hydralazine (10(-5) mol/l), a strong antioxidant, ameliorated tolerance to IS-5-MN, but did not affect the absence of tolerance to either ketoxime. The minimum lethal dose in rat for 50-IS-2-MN and 20-IS-5-MN was greater than 1000 mg/kg. Conclusion: These results suggest that the modification of the configuration at the ester carbon of IS-5-MN contributes to more potent and tolerance-devoid activity on the rat superior mesenteric artery.",
publisher = "ECV-Editio Cantor Verlag Medizin Naturwissenschaften, Aulendorf",
journal = "Arzneimittelforschung - Drug Research",
title = "Comparison of vasorelaxant effect and tolerance profile of a novel isosorbide-5-mononitrate derivative with its stereoisomer and parent drug on rat mesenteric artery",
volume = "60",
number = "4",
pages = "189-197",
doi = "10.1055/s-0031-1296272",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1337"
}

Stepanović-Petrović, R., Savić, V., Tomić, M., Tokić-Vujošević, Z., Simić, M., Stepanović, J. M., Jokanović, M.,& Micov, A.. (2010). Comparison of vasorelaxant effect and tolerance profile of a novel isosorbide-5-mononitrate derivative with its stereoisomer and parent drug on rat mesenteric artery. in Arzneimittelforschung - Drug Research
ECV-Editio Cantor Verlag Medizin Naturwissenschaften, Aulendorf., 60(4), 189-197.
https://doi.org/10.1055/s-0031-1296272
https://hdl.handle.net/21.15107/rcub_farfar_1337

Stepanović-Petrović R, Savić V, Tomić M, Tokić-Vujošević Z, Simić M, Stepanović JM, Jokanović M, Micov A. Comparison of vasorelaxant effect and tolerance profile of a novel isosorbide-5-mononitrate derivative with its stereoisomer and parent drug on rat mesenteric artery. in Arzneimittelforschung - Drug Research. 2010;60(4):189-197.
doi:10.1055/s-0031-1296272
https://hdl.handle.net/21.15107/rcub_farfar_1337 .

Stepanović-Petrović, Radica, Savić, Vladimir, Tomić, Maja, Tokić-Vujošević, Zorana, Simić, Milena, Stepanović, Jelena M., Jokanović, Milan, Micov, Ana, "Comparison of vasorelaxant effect and tolerance profile of a novel isosorbide-5-mononitrate derivative with its stereoisomer and parent drug on rat mesenteric artery" in Arzneimittelforschung - Drug Research, 60, no. 4 (2010):189-197,
https://doi.org/10.1055/s-0031-1296272 .,
https://hdl.handle.net/21.15107/rcub_farfar_1337 .

TY  - JOUR
AU  - Tomić, Maja
AU  - Vučković, Sonja M.
AU  - Stepanović-Petrović, Radica
AU  - Ugrešić, Nenad
AU  - Prostran, Milica
AU  - Bošković, Bogdan
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1375
AB  - BACKGROUND: Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components. METHODS: The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis. RESULTS: Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50). CONCLUSIONS: The, synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain. (Anesth Analg 2010;110:1198-1205)
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents
VL  - 110
IS  - 4
SP  - 1198
EP  - 1205
DO  - 10.1213/ANE.0b013e3181cbd8da
ER  - 

@article{
author = "Tomić, Maja and Vučković, Sonja M. and Stepanović-Petrović, Radica and Ugrešić, Nenad and Prostran, Milica and Bošković, Bogdan",
year = "2010",
abstract = "BACKGROUND: Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components. METHODS: The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis. RESULTS: Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50). CONCLUSIONS: The, synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain. (Anesth Analg 2010;110:1198-1205)",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
title = "Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents",
volume = "110",
number = "4",
pages = "1198-1205",
doi = "10.1213/ANE.0b013e3181cbd8da"
}

Tomić, M., Vučković, S. M., Stepanović-Petrović, R., Ugrešić, N., Prostran, M.,& Bošković, B.. (2010). Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 110(4), 1198-1205.
https://doi.org/10.1213/ANE.0b013e3181cbd8da

Tomić M, Vučković SM, Stepanović-Petrović R, Ugrešić N, Prostran M, Bošković B. Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents. in Anesthesia and Analgesia. 2010;110(4):1198-1205.
doi:10.1213/ANE.0b013e3181cbd8da .

Tomić, Maja, Vučković, Sonja M., Stepanović-Petrović, Radica, Ugrešić, Nenad, Prostran, Milica, Bošković, Bogdan, "Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents" in Anesthesia and Analgesia, 110, no. 4 (2010):1198-1205,
https://doi.org/10.1213/ANE.0b013e3181cbd8da . .

TY  - JOUR
AU  - Tomić, Maja
AU  - Vučković, Sonja M.
AU  - Stepanović-Petrović, Radica
AU  - Micov, Ana
AU  - Ugrešić, Nenad
AU  - Prostran, Milica
AU  - Bošković, Bogdan
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1387
AB  - Antiepileptic and antidepressant drugs are the primary treatments for pain relief in diabetic neuropathy. Combination therapy is a valid approach in pain treatment, where a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of two-drug combinations of gabapentin, oxcarbazepine, and amitriptyline on nociception in diabetic mice and aimed to determine the type of interaction between components. The nociceptive responses in normal and diabetic mice were assessed by the tail-flick test. The testing was performed before and three weeks after the diabetes induction with streptozotocin (150 mg/kg; i.p.), when the antinociceptive effects of gabapentin, oxcarbazepine, amitriptyline and their two-drug combinations were examined. Gabapentin (10-40 mg/kg; p.o.) and oxcarbazepine (20-80 mg/kg; p.o.) produced a significant, dose-dependent antinociception in diabetic mice while amitriptyline (5-60 mg/kg; p.o.) produced weak antinociceptive effect. In normal mice, neither of the drugs produced antinociception. Gabapentin and oxcarbazepine, co-administered in fixed-dose fractions of the ED(50) to diabetic mice, induced significant, dose-dependent antinociception. Isobolographic analysis revealed synergistic interaction. Oxcarbazepine (10-60mg/kg; p.o.)+amitriptyline (5mg/kg; p.o.) and gabapentin (10-30mg/kg: p.o.)+amitriptyline (5mg/kg; p.o.) combinations significantly and close-dependently reduced nociception in diabetic mice. Analysis of the log dose-response curves for oxcarbazepine or gabapentin in a presence of amitriptyline and oxcarbazepine or gabapentin applied alone, revealed a synergism in oxcarbazepine-amitriptyline and additivity in gabapentin-amitriptyline combination. These findings provide new information about the combination therapy of painful diabetic neuropathy and should be explored further in patients with diabetic neuropathy.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmacology
T1  - Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice
VL  - 628
IS  - 1-3
SP  - 75
EP  - 82
DO  - 10.1016/j.ejphar.2009.11.016
ER  - 

@article{
author = "Tomić, Maja and Vučković, Sonja M. and Stepanović-Petrović, Radica and Micov, Ana and Ugrešić, Nenad and Prostran, Milica and Bošković, Bogdan",
year = "2010",
abstract = "Antiepileptic and antidepressant drugs are the primary treatments for pain relief in diabetic neuropathy. Combination therapy is a valid approach in pain treatment, where a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of two-drug combinations of gabapentin, oxcarbazepine, and amitriptyline on nociception in diabetic mice and aimed to determine the type of interaction between components. The nociceptive responses in normal and diabetic mice were assessed by the tail-flick test. The testing was performed before and three weeks after the diabetes induction with streptozotocin (150 mg/kg; i.p.), when the antinociceptive effects of gabapentin, oxcarbazepine, amitriptyline and their two-drug combinations were examined. Gabapentin (10-40 mg/kg; p.o.) and oxcarbazepine (20-80 mg/kg; p.o.) produced a significant, dose-dependent antinociception in diabetic mice while amitriptyline (5-60 mg/kg; p.o.) produced weak antinociceptive effect. In normal mice, neither of the drugs produced antinociception. Gabapentin and oxcarbazepine, co-administered in fixed-dose fractions of the ED(50) to diabetic mice, induced significant, dose-dependent antinociception. Isobolographic analysis revealed synergistic interaction. Oxcarbazepine (10-60mg/kg; p.o.)+amitriptyline (5mg/kg; p.o.) and gabapentin (10-30mg/kg: p.o.)+amitriptyline (5mg/kg; p.o.) combinations significantly and close-dependently reduced nociception in diabetic mice. Analysis of the log dose-response curves for oxcarbazepine or gabapentin in a presence of amitriptyline and oxcarbazepine or gabapentin applied alone, revealed a synergism in oxcarbazepine-amitriptyline and additivity in gabapentin-amitriptyline combination. These findings provide new information about the combination therapy of painful diabetic neuropathy and should be explored further in patients with diabetic neuropathy.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmacology",
title = "Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice",
volume = "628",
number = "1-3",
pages = "75-82",
doi = "10.1016/j.ejphar.2009.11.016"
}

Tomić, M., Vučković, S. M., Stepanović-Petrović, R., Micov, A., Ugrešić, N., Prostran, M.,& Bošković, B.. (2010). Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice. in European Journal of Pharmacology
Elsevier Science BV, Amsterdam., 628(1-3), 75-82.
https://doi.org/10.1016/j.ejphar.2009.11.016

Tomić M, Vučković SM, Stepanović-Petrović R, Micov A, Ugrešić N, Prostran M, Bošković B. Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice. in European Journal of Pharmacology. 2010;628(1-3):75-82.
doi:10.1016/j.ejphar.2009.11.016 .

Tomić, Maja, Vučković, Sonja M., Stepanović-Petrović, Radica, Micov, Ana, Ugrešić, Nenad, Prostran, Milica, Bošković, Bogdan, "Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice" in European Journal of Pharmacology, 628, no. 1-3 (2010):75-82,
https://doi.org/10.1016/j.ejphar.2009.11.016 . .

TY  - JOUR
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Popović, B.
AU  - Stepanović-Petrović, Radica
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1338
AB  - BACKGROUND AND PURPOSE Levetiracetam, a novel antiepileptic drug, has recently been shown to have antinociceptive effects in various animal models of pain. The purpose of this study was to investigate the antihyperalgesic effect of levetiracetam and its mechanism of action, by examining the involvement of GABAergic, opioidergic, 5-hydroxytryptaminergic (5-HTergic) and adrenergic systems in its effect, in a rat model of inflammatory pain. EXPERIMENTAL APPROACH Rats were intraplantarly injected with the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of levetiracetam on carrageenan-induced hyperalgesia; and (ii) the effects of bicuculline (selective GABA(A) receptor antagonist), naloxone (non-selective opioid receptor antagonist), methysergide (non-selective 5-HT receptor antagonist) and yohimbine (selective alpha(2)-adrenoceptor antagonist) on the antihyperalgesic action of levetiracetam. RESULTS Levetiracetam (10-200 mg center dot kg-1; p.o.) significantly reduced, in a dose-dependent manner, the inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of levetiracetam was significantly decreased after administration of bicuculline (0.5-2 mg center dot kg-1; i.p.), naloxone (1-3 mg center dot kg-1; i.p.), methysergide (0.25-1 mg center dot kg-1; i.p.) and yohimbine (1-3 mg center dot kg-1; i.p.). CONCLUSIONS AND IMPLICATIONS These results show that levetiracetam produced antihyperalgesia which is at least in part mediated by GABA(A), opioid, 5-HT and alpha(2)-adrenergic receptors, in an inflammatory model of pain. The efficacy of levetiracetam in this animal model of inflammatory pain suggests that it could be a potentially important agent for treating inflammatory pain conditions in humans.
PB  - Wiley-Blackwell, Malden
T2  - British Journal of Pharmacology
T1  - The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action
VL  - 161
IS  - 2
SP  - 384
EP  - 392
DO  - 10.1111/j.1476-5381.2010.00877.x
ER  - 

@article{
author = "Micov, Ana and Tomić, Maja and Popović, B. and Stepanović-Petrović, Radica",
year = "2010",
abstract = "BACKGROUND AND PURPOSE Levetiracetam, a novel antiepileptic drug, has recently been shown to have antinociceptive effects in various animal models of pain. The purpose of this study was to investigate the antihyperalgesic effect of levetiracetam and its mechanism of action, by examining the involvement of GABAergic, opioidergic, 5-hydroxytryptaminergic (5-HTergic) and adrenergic systems in its effect, in a rat model of inflammatory pain. EXPERIMENTAL APPROACH Rats were intraplantarly injected with the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of levetiracetam on carrageenan-induced hyperalgesia; and (ii) the effects of bicuculline (selective GABA(A) receptor antagonist), naloxone (non-selective opioid receptor antagonist), methysergide (non-selective 5-HT receptor antagonist) and yohimbine (selective alpha(2)-adrenoceptor antagonist) on the antihyperalgesic action of levetiracetam. RESULTS Levetiracetam (10-200 mg center dot kg-1; p.o.) significantly reduced, in a dose-dependent manner, the inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of levetiracetam was significantly decreased after administration of bicuculline (0.5-2 mg center dot kg-1; i.p.), naloxone (1-3 mg center dot kg-1; i.p.), methysergide (0.25-1 mg center dot kg-1; i.p.) and yohimbine (1-3 mg center dot kg-1; i.p.). CONCLUSIONS AND IMPLICATIONS These results show that levetiracetam produced antihyperalgesia which is at least in part mediated by GABA(A), opioid, 5-HT and alpha(2)-adrenergic receptors, in an inflammatory model of pain. The efficacy of levetiracetam in this animal model of inflammatory pain suggests that it could be a potentially important agent for treating inflammatory pain conditions in humans.",
publisher = "Wiley-Blackwell, Malden",
journal = "British Journal of Pharmacology",
title = "The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action",
volume = "161",
number = "2",
pages = "384-392",
doi = "10.1111/j.1476-5381.2010.00877.x"
}

Micov, A., Tomić, M., Popović, B.,& Stepanović-Petrović, R.. (2010). The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action. in British Journal of Pharmacology
Wiley-Blackwell, Malden., 161(2), 384-392.
https://doi.org/10.1111/j.1476-5381.2010.00877.x

Micov A, Tomić M, Popović B, Stepanović-Petrović R. The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action. in British Journal of Pharmacology. 2010;161(2):384-392.
doi:10.1111/j.1476-5381.2010.00877.x .

Micov, Ana, Tomić, Maja, Popović, B., Stepanović-Petrović, Radica, "The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action" in British Journal of Pharmacology, 161, no. 2 (2010):384-392,
https://doi.org/10.1111/j.1476-5381.2010.00877.x . .

TY  - JOUR
AU  - Stepanović-Petrović, Radica
AU  - Tomić, Maja
AU  - Vučković, Sonja M.
AU  - Kocev, Nikola
AU  - Ugrešić, Nenad
AU  - Prostran, Milica
AU  - Bošković, Bogdan
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1092
AB  - Background/Aims: The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline ( GABA A receptor antagonist) on these effects of antiepileptic drugs. 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 carbamazepine/ oxcarbazepine on Con A-induced hyperalgesia, and ( 3) the effects of bicuculline on the carbamazepine/ oxcarbazepine antihyperalgesia. Results: Intraperitoneally injected bicuculline (0.5 - 1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine ( 27 mg/ kg, i.p.) and oxcarbazepine ( 80 mg/ kg, i.p.). When applied intraplantarly, bicuculline ( 0.14 mg/ paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine ( 0.14 mg/ paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. Conclusion: These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA A receptor activation. Copyright
PB  - Karger, Basel
T2  - Pharmacology
T1  - GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia
VL  - 82
IS  - 1
SP  - 53
EP  - 58
DO  - 10.1159/000127841
ER  - 

@article{
author = "Stepanović-Petrović, Radica and Tomić, Maja and Vučković, Sonja M. and Kocev, Nikola and Ugrešić, Nenad and Prostran, Milica and Bošković, Bogdan",
year = "2008",
abstract = "Background/Aims: The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline ( GABA A receptor antagonist) on these effects of antiepileptic drugs. 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 carbamazepine/ oxcarbazepine on Con A-induced hyperalgesia, and ( 3) the effects of bicuculline on the carbamazepine/ oxcarbazepine antihyperalgesia. Results: Intraperitoneally injected bicuculline (0.5 - 1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine ( 27 mg/ kg, i.p.) and oxcarbazepine ( 80 mg/ kg, i.p.). When applied intraplantarly, bicuculline ( 0.14 mg/ paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine ( 0.14 mg/ paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. Conclusion: These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA A receptor activation. Copyright",
publisher = "Karger, Basel",
journal = "Pharmacology",
title = "GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia",
volume = "82",
number = "1",
pages = "53-58",
doi = "10.1159/000127841"
}

Stepanović-Petrović, R., Tomić, M., Vučković, S. M., Kocev, N., Ugrešić, N., Prostran, M.,& Bošković, B.. (2008). GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia. in Pharmacology
Karger, Basel., 82(1), 53-58.
https://doi.org/10.1159/000127841

Stepanović-Petrović R, Tomić M, Vučković SM, Kocev N, Ugrešić N, Prostran M, Bošković B. GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia. in Pharmacology. 2008;82(1):53-58.
doi:10.1159/000127841 .

Stepanović-Petrović, Radica, Tomić, Maja, Vučković, Sonja M., Kocev, Nikola, Ugrešić, Nenad, Prostran, Milica, Bošković, Bogdan, "GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia" in Pharmacology, 82, no. 1 (2008):53-58,
https://doi.org/10.1159/000127841 . .

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 . .