INFLUENCE OF AMINOPHYLLINE AND STRYCHNINE ON THE PROTECTIVE ACTIVITY OF EXCITATORY AMINO-ACID ANTAGONISTS AGAINST MAXIMAL ELECTROSHOCK-INDUCED CONVULSIONS IN MICE

Aminophylline reversed the protective action of both, (2-carboxypipera zine-4-yl)-1-propenyl-1-phosphonic acid (D-CPP-ene - a competitive NMD A antagonist) and valproate (used as a conventional antiepileptic drug for comparative purposes) against maximal electroshock-induced seizur es. The respective ED(50) values of aminophylline were 55.7 and 98.4 m g/kg i.p. However, aminophylline (up to 100 mg/kg i.p.) did not influe nce the protective efficacy of -4-methyl-7,8-methylenedioxy-5H-2,3-ben zodiazepine (GYKI 52466 - a non-NMDA antagonist). Strychnine affected the protection provided by D-CPP-ene, GYKI 52466, and valproate agains t maximal electroshock - the ED(50) values of strychnine for the rever sal of the anticonvulsive effects of D-CPP-ene, GYKI 52466 or valproat e were 0.082, 0.35 and 0.28 mg/kg s.c., respectively. An involvement o f strychnine sensitive glycinergic receptor-mediated events in the mec hanism of the anticonvulsive activity of excitatory amino acid antagon ists and valproate may be postulated. The ineffectiveness of aminophyl line to reduce the anticonvulsive effects of GYKI 52466 may distinguis h a new class of antiepileptic drugs offering an advantage over conven tional antiepileptics in patients with epilepsy, requiring aminophylli ne for pulmonary reasons.