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

Adenosine has been demonstrated to have an anticonvulsant action which is mediated predominantly by the adenosine A(1) receptor subtype. The present study was conducted to determine if the adenosinergic system and adenosine A(1) receptors are involved in the anticonvulsant action of the antiepileptic drugs phenobarbitone and carbamazepine, in pentylenetetrazole (PTZ)-induced 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 antiepileptic drugs. However, the nonspecific adenosine receptor antagonists, theophylline (50 and 100 mg/kg i.p.), reserved the anticonvulsant action of carbamazepine completely and that of phenobarbitone partially. This suggests that adenosine A(1) receptors do not mediate the anticonvulsant effects of these agents. When phenobarbitone/carbamazepine were coadministered with adenosine/N-6-cyclopentyladenosine (CPA), a specific adenosine A(1) receptor agonist, an enhancement in protection against PTZ-induced seizures was observed. The diversity of anticonvulsant mechanism of carbamazepine/phenobarbitone and that of adenosinergic agents could be responsible for this effect. (C) 1999 Prous Science. All rights reserved.