The effects of alpha2-adrenoceptor agents on anti-hyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory pain.
In this study, the effects of yohimbine (alpha2-adrenoceptor antagonist) and clonidine (alpha2-adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic alpha2-receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated.
Vucković
Sonja M
SM
Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Serbia and Montenegro. svuckovic@med.bg.ac.yu
Tomić
Maja A
MA
Stepanović-Petrović
Radica M
RM
Ugresić
Nenad
N
Prostran
Milica S
MS
Bosković
Bogdan
B
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000818:Animals; D002220:Carbamazepine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D003208:Concanavalin A; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D000078330:Oxcarbazepine; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D018712:Analgesics, Non-Narcotic; D003208:Concanavalin A; D002220:Carbamazepine; D000078330:Oxcarbazepine