The anti-hyperalgesic effects of carbamazepine and oxcarbazepine are attenuated by treatment with adenosine receptor antagonists.
The antinociceptive effects of carbamazepine and oxcarbazepine, and the influence of caffeine, were examined in a paw pressure test in rats. Carbamazepine (10-40 mg/kg; intraperitoneal, 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 (i.p1.). A comparable pattern of antinociceptive effect of carbamazepine and oxcarbazepine was observed; the only difference is their potency, in that carbamazepine was about three times more potent than oxcarbazepine. Caffeine (5-20mg/kg; i.p.), a non-selective adenosine receptor antagonist, significantly depressed the antinociceptive effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Also, a significant depression of the antinociceptive effects of carbamazepine and oxcarbazepine was observed by pretreatment with 1,3-dipropyl-8-cyclopentylxantine (DPCPX, 0.4 and 0.8 mg/kg; i.p.), an adenosine A(1) receptor antagonist. These findings indicate that, in a paw inflammatory hyperalgesia in rats, the antinociceptive effects of both drugs are, at least partially, mediated by adenosine A(1) receptors. In conclusion, the present study suggests the potential clinical importance of carbamazepine and oxcarbazepine in the treatment of inflammatory pain. In addition, caffeine consumption could possibly depress the analgesic effects of both anticonvulsive drugs.
Tomić
Maja A
MA
Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia and Montenegro Department of Clinical Pharmacology, Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia and Montenegro Medical Military Academy, Belgrade, Serbia and Montenegro.
Vučković
Sonja M
SM
Stepanović-Petrović
Radica M
RM
Ugrešić
Nenad
N
Prostran
Milica Š
MŠ
Bošković
Bogdan
B
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D000078330:Oxcarbazepine; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology
D018712:Analgesics, Non-Narcotic; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D002220:Carbamazepine; D002110:Caffeine; D000078330:Oxcarbazepine