EXCITOPROTECTIVE EFFECT OF FELBAMATE IN CULTURED CORTICAL-NEURONS

The effect of felbamate on excitatory amino acid-induced biochemical c hanges was investigated in cultured cortical neurons. Felbamate inhibi ted NMDA- and glutamate-induced neuronal injury in a dose-dependent ma nner, 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 o f glycine failed to modulate the effect of felbamate on NMDA-induced n eurotoxicity 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 su ggest that felbamate acts through a site on the NMDA receptor that is distinct from the strychnine-insensitive site, and that the effect of the drug on neuronal Ca2+ may be pivotal to its neuroprotective mechan ism.