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.
MeSH terms
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Animals
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Anticonvulsants / pharmacology*
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Binding Sites / physiology
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Calcium / metabolism
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Cell Death / drug effects
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Cells, Cultured / drug effects
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Cerebral Cortex / cytology*
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Felbamate
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Glycine / antagonists & inhibitors
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Kainic Acid / pharmacology
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Kynurenic Acid / analogs & derivatives
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Kynurenic Acid / pharmacology
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N-Methylaspartate / pharmacology
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Neurons / cytology
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Neurons / drug effects*
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Neuroprotective Agents / pharmacology*
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Neurotoxins / pharmacology
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Phenylcarbamates
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Propylene Glycols / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / agonists
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Strychnine / metabolism
Substances
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Anticonvulsants
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Neuroprotective Agents
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Neurotoxins
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Phenylcarbamates
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Propylene Glycols
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Receptors, N-Methyl-D-Aspartate
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N-Methylaspartate
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Kynurenic Acid
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Strychnine
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Kainic Acid
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Calcium
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5,7-dichlorokynurenic acid
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Glycine
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Felbamate