Excitoprotective effect of felbamate in cultured cortical neurons.
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.
Kanthasamy
A G
AG
Department of Neurology, University of California Irvine 92717, USA.
Matsumoto
R R
RR
Gunasekar
P G
PG
Trunong
D D
DD
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000078328:Felbamate; D005998:Glycine / Q000037:antagonists & inhibitors; D007608:Kainic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D013331:Strychnine / Q000378:metabolism
D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D048448:Phenylcarbamates; D011409:Propylene Glycols; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D007736:Kynurenic Acid; D013331:Strychnine; D007608:Kainic Acid; D002118:Calcium; C066192:5,7-dichlorokynurenic acid; D005998:Glycine; D000078328:Felbamate