Chlormethiazole anticonvulsive efficacy diminished by N-methyl-D-aspartate but not kainate in mice

Eur J Pharmacol. 1998 Mar 26;345(3):257-60. doi: 10.1016/s0014-2999(98)00128-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / analogs & derivatives
  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Anticonvulsants / pharmacology*
  • Chlormethiazole / pharmacology*
  • Electroshock
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Kainic Acid / pharmacology*
  • Male
  • Mice
  • N-Methylaspartate / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Seizures / chemically induced
  • Seizures / physiopathology

Substances

  • Anticonvulsants
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Chlormethiazole
  • 2-amino-4-methyl-5-phosphono-3-pentenoic acid
  • N-Methylaspartate
  • 2-Amino-5-phosphonovalerate
  • Kainic Acid