ADENOSINERGIC MECHANISMS IN ANTICONVULSANT ACTION OF DIAZEPAM AND SODIUM VALPROATE

The effects of adenosine receptor agonists and antagonists were studie d in pentylenetetrazole (PTZ)-induced seizures in rats. Animals were p retreated with the non-specific adenosine receptor antagonist, theophy lline (50 and 100 mg/kg, i.p.), or the specific A(1) adenosine recepto r antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), in a dose of 1 mg/kg, i.p., followed by 100% anticonvulsant doses of diazepam (4 m g/kg)/sodium valproate (300 mg/kg, i.p.). Subsequently, they were chal lenged with convulsant doses of PTZ i.e. 60 mg/kg, i.p. It was seen th at while DPCPX could not reverse the protection of both the antiepilep tic drugs, theophylline significantly reversed this protection, as ass essed by percent incidence of seizures and change in latency parameter s. In another set of experiments, the rats were pretreated with a comb ination of subanticonvulsant doses of adenosine (500 mg/kg) or specifi c adenosine A(1) receptor agonist, cyclopentyladenosine (CPA) and diaz epam (0.5 and 1 mg/kg)/sodium valproate (150 mg/kg), prior to PTZ chal lenge. We observed a decrease in incidence and increase in latency of seizures following either combination. The protection observed was ind ependent of the hypothermic and hypotensive effects of adenosine and C PA. These results indicate that though A(1) agonist enhances the prote ction of diazepam and sodium valproate, a direct involvement of adenos ine A(1) receptor in anticonvulsant action of these drugs is doubtful.