Effect of adenosinergic modulation on the anticonvulsant effect of phenobarbitone and carbamazepine

Adenosine has been demonstrated to have an anticonvulsant action which is m ediated predominantly by the adenosine A(1) receptor subtype. The present s tudy was conducted to determine if the adenosinergic system and adenosine A (1) receptors are involved in the anticonvulsant action of the antiepilepti c drugs phenobarbitone and carbamazepine, in pentylenetetrazole (PTZ)-induc ed seizures in rats. The specific adenosine A(1) receptor antagonist, DPCPX (1 mg/kg i.p.), had no effect on the anticonvulsant action of the two anti epileptic drugs. However, the nonspecific adenosine receptor antagonists, t heophylline (50 and 100 mg/kg i.p.), reserved the anticonvulsant action of carbamazepine completely and that of phenobarbitone partially. This suggest s that adenosine A(1) receptors do not mediate the anticonvulsant effects o f these agents. When phenobarbitone/carbamazepine were coadministered with adenosine/N-6-cyclopentyladenosine (CPA), a specific adenosine A(1) recepto r agonist, an enhancement in protection against PTZ-induced seizures was ob served. The diversity of anticonvulsant mechanism of carbamazepine/phenobar bitone and that of adenosinergic agents could be responsible for this effec t. (C) 1999 Prous Science. All rights reserved.