Excitoprotective effect of felbamate in cultured cortical neurons

Brain Res. 1995 Dec 24;705(1-2):97-104. doi: 10.1016/0006-8993(95)01147-1.

Abstract

The effect of felbamate on excitatory amino acid-induced biochemical changes was investigated in cultured cortical neurons. Felbamate inhibited NMDA- and glutamate-induced neuronal injury in a dose-dependent manner, but it did not rescue cells from kainate-induced neurotoxicity. The neuroprotective effect was accompanied by a decrease in NMDA- and glutamate-induced neuronal calcium (Ca2+) influx. Exogenous addition of glycine failed to modulate the effect of felbamate on NMDA-induced neurotoxicity or Ca2+ influx, although corresponding changes induced by the strychnine-insensitive glycine antagonist, 5,7-dichlorokynurenic acid could be modulated with glycine. Taken together, these results suggest that felbamate acts through a site on the NMDA receptor that is distinct from the strychinine-insensitive site, and that the effect of the drug on neuronal Ca2+ may be pivotal to its neuroprotective mechanism.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Binding Sites / physiology
  • Calcium / metabolism
  • Cell Death / drug effects
  • Cells, Cultured / drug effects
  • Cerebral Cortex / cytology*
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Felbamate
  • Glycine / antagonists & inhibitors
  • Kainic Acid / pharmacology
  • Kynurenic Acid / analogs & derivatives
  • Kynurenic Acid / pharmacology
  • N-Methylaspartate / pharmacology
  • Neurons / cytology
  • Neurons / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins / pharmacology
  • Phenylcarbamates
  • Propylene Glycols / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Strychnine / metabolism

Substances

  • Anticonvulsants
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Neurotoxins
  • Phenylcarbamates
  • Propylene Glycols
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • Kynurenic Acid
  • Strychnine
  • Kainic Acid
  • Calcium
  • 5,7-dichlorokynurenic acid
  • Glycine
  • Felbamate