GYKI-52466 4-METHOXY-7,8-METHYLENEDIOXY-5H-2,3-BENZODIAZEPINE HYDROCHLORIDE] AND THE ANTICONVULSIVE ACTIVITY OF CONVENTIONAL ANTIEPILEPTICSAGAINST PENTETRAZOL IN MICE

Excitatory amino acids participate in the generation of seizure activi ty. Consequently, the effects of GYKI 52466 4-methoxy-7,8-methylenedio xy-5H-2,3-benzodiazepine hydrochloride], an antagonist of glutamate-me diated events, on the protective activity of conventional antiepilepti c drugs against pentetrazol were studied. GYKI 52466 (up to 10 mg/kg, ip) did not affect the clonic phase of pentetrazol (injected sc at its CD97 Of 90 mg/kg) convulsions. Only the antipentetrazol activity of v alproate (100 mg/kg) was enhanced by GYKI 52466 (10 mg/kg)-the percent age of mice protected was significantly increased from 20 to 90%. The anticonvulsive activity of clonazepam (at 0.01), ethosuximide (at 50), and phenobarbital (at 2.5 mg/kg) was not modified by GYKI 52466 (up t o 10 mg/kg). The combination of valproate (100 mg/kg) with GM(I 52466 (10 mg/kg) did not affect the performance of mice evaluated in the chi mney test. However, this combination resulted in significant memory de ficits, measured in the passive avoidance task. In no case did GYKI 52 466 (10 mg/kg) affect either total or free plasma levels of antiepilep tic drugs las measured by immunofluorescence), so a pharmacokinetic in teraction is not probable. Finally, the interaction of the non-NMDA re ceptor antagonist with antiepileptic drugs does not seem promising in the pentetrazol test, recognized as a model of human myoclonic epileps y.