Influence of CGS 15943 A (a nonxanthine adenosine antagonist) on the protection offered by a variety of antiepileptic drugs against maximal electroshock-induced seizures in mice

Abstract

CGS 15943 A (a nonxanthine adenosine antagonist) was studied on the protective efficacy of carbamazepine (60 min prior to the convulsive test), diazepam (60 min), diphenylhydantoin (120 min), phenobarbital (120 min), and valproate (30 min) against maximal electroshock-induced convulsions in mice. Moreover, the influence of the adenosine antagonist on 2-chloroadenosine (1 mg/kg, 20 min prior to the test)- and valproate (250 mg/kg, 30 min)-induced inhibitions of locomotor activity was also studied. CGS 15943 A (1 mg/kg) was given 15 min before both tests and all the drugs were administered i.p.. The adenosine antagonist (1 mg/kg) remained without influence upon the protective activity of all studied antiepileptics, reflected by their respective ED50 values against maximal electroshock. However, both 2-chloroadenosine and valproate-induced inhibitions of locomotor activity were attenuated by CGS 15943 A, which alone did not affect this parameter. However, CGS 15943 A (5 mg/kg) diminished the protection offered by diphenylhydantoin, increasing its ED50 value from 13 to 16 mg/kg. It may be concluded that the protection provided by common antiepileptic drugs against electroconvulsions seems independent of adenosine-mediated inhibition. In the case of diphenylhydantoin, one may suggest the involvement of purinergic transmission in the final anticonvulsant effect.