The antiepileptic drugs phenytoin, valproic acid and phenobarbital were examined for their ability to inhibit N-methyl-D-aspartate (NMDA)-stimulated [3H]norepinephrine efflux from rat brain cortical slices. All three drugs inhibited efflux at varying concentrations. Valproic acid was the most potent and inhibited efflux at 0.01 mg/ml. Phenytoin and phenobarbital inhibited efflux at 0.1 mg/ml. These results indicate that some antiepileptic drugs are capable of inhibiting NMDA receptor function in the therapeutic range.
