INFLUENCE OF A CA2+ CHANNEL AGONIST, BAY K-8644, ON THE ANTICONVULSANT ACTIVITY OF NMDA AND NON-NMDA RECEPTOR ANTAGONISTS

Bay k-8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methylphenyl)-pyridine-5-carboxylate) (a Ca2+ channel agonist of the dihydropyridine class) at 5 mg/kg (s.c.) impaired the anticonvulsant activities of two competitive NMDA receptor antagonists, CGP 37849 (D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid) and D-CPP-ene (3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid) (given i.p.), against electroconvulsions. In contrast, the Ca2+ channel agonist did not affect the protection afforded by the AMPA receptor antagonists, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline) and GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-5-2,3-benzodiazepine), or by a non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), all being injected i.p. It may be concluded that the anticonvulsive activity of competitive NMDA receptor antagonists can be impaired by Ca2+ ion influx.