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.
Czuczwar
S J
SJ
Department of Pharmacology and Toxicology, Medical School, Lublin, Poland.
Gasior
M
M
Turski
W A
WA
Kleinrok
Z
Z
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D004597:Electroshock; D008297:Male; D051379:Mice; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D000927:Anticonvulsants; D015220:Calcium Channels; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium