Chlormethiazole anticonvulsive efficacy diminished by N-methyl-D-aspartate but not kainate in mice.
The aim of this study was to evaluate the effect of N-methyl-D-aspartate (NMDA) and kainate used at nonconvulsive doses upon protective efficacy of chlormethiazole against maximal electroshock-induced seizures. NMDA (50 mg/kg, i.p.) reduced the anticonvulsant potency of chlormethiazole increasing its ED50 value from 126.9 to 155.0 mg/kg. The effect of NMDA was completely reversed by the competitive NMDA receptor antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 40116) (0.06 mg/kg i.p.). Kainic acid (9 mg/kg i.p.) did not affect the anticonvulsive properties of chlormethiazole. Our results suggest that NMDA but not kainate receptor-mediated events participate in the anticonvulsant action of chlormethiazole.
Pilip
S
S
Department of Pharmacology and Toxicology, Medical University School, Lublin, Poland.
Urbanska
E M
EM
Czuczwar
S J
SJ
Kleinrok
Z
Z
Turski
W A
WA
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002719:Chlormethiazole / Q000494:pharmacology*; D004597:Electroshock; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D002719:Chlormethiazole; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D007608:Kainic Acid