Vučković, Sonja (7003869333)Sonja (7003869333)VučkovićTomić, M. (7006939166)M. (7006939166)TomićStepanović-Petrović, R. (6506683297)R. (6506683297)Stepanović-PetrovićUgrešić, N. (6602152735)N. (6602152735)UgrešićProstran, M. (7004009031)M. (7004009031)ProstranBošković, B. (7004055023)B. (7004055023)Bošković2025-06-132025-06-132007https://doi.org/10.1358/mf.2007.29.10.1147773https://www.scopus.com/inward/record.uri?eid=2-s2.0-39149128222&doi=10.1358%2fmf.2007.29.10.1147773&partnerID=40&md5=9993e3887cd5c043b64a9eb76c5ca194https://remedy.med.bg.ac.rs/handle/123456789/10844The anticonvulsant carbamazepine was recently shown to possess local peripheral antinociceptive properties. In this study, we investigated whether α2-adrenergic receptors are involved in the local peripheral antihyperalgesic effects of carbamazepine and determined the type of interaction between carbamazepine and clonidine, an α2-adrenoceptor agonist. Intraplantar (i.pl.) coadministration of either carbamazepine (100-1000 nmol/paw) or clonidine (1.9-3.7 nmol/paw) with the proinflammatory compound concanavalin A (Con A; 0.8 mg/paw) caused a significant dose- and time-dependent reduction of the difference between the forces exerted by a rat's hind paws in a modified paw-pressure test. The coadministration of 260 and 520 nmol/paw (i.pl.) yohimbine, an α2-adrenoceptor antagonist, with carbamazepine, significantly depressed the local antihyperalgesic effect in a dose- and time-dependent manner whereas yohimbine by itself did not have any effect. The administration of a mixture of carbamazepine and clonidine at fixed dose fractions (1/4, 1/2 and 3/4) of ED50 caused a significant and dose-dependent reduction of Con A-induced hyperalgesia. Isobolographic analysis revealed an additive interaction. These results suggest that α2-adrenoceptors play a role in the local peripheral antihyperalgesic effects of carbamazepine and that local peripheral coadministration of carbamazepine with clonidine results in an additive antihyperalgesic effect. © 2007 Prous Science. All rights reserved.Additive interactionCarbamazepineClonidineInflammatory hyperalgesiaIsobolographic analysisLocal administrationPeripheral α2-adrenoceptorsYohimbine