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.