The anticonvulsant compound oxcarbazepine and its principal 10-monohydroxy metabolite protected potently against electroshock-induced tonic hindlimb extension. Maximal plasma concentrations depended on dose and were reached < or = 1 h after an oral dose of oxcarbazepine and < 2 h after monohydroxy derivative. In mice, the ED50 was 14 mg/kg for oxcarbazepine and 20.5 mg/kg for the monohydroxy derivative, p.o. In rats, the ED50 was 13.5 mg/kg for oxcarbazepine and 17.0 mg/kg for monohydroxy derivative, p.o. This protective effect compared favorably with the efficacy of carbamazepine, phenytoin, phenobarbital and diazepam in the same test. As observed previously, valproate and ethosuximide were markedly less potent. The effect of oxcarbazepine and its monohydroxy derivative on sustained high frequency repetitive firing of sodium-dependent action potentials of mouse spinal cord neurons in cell culture was also examined using intracellular recording techniques. Both compounds reduced the percentage of neurons capable of sustained action potential firing in concentration-dependent manner. The EC50 for oxcarbazepine was 5 x 10(-8) M and that for monohydroxy derivative was 2 x 10(-8) M (P > 0.05 vs. oxcarbazepine). For comparison, the EC50 for carbamazepine was significantly higher (6 x 10(-7) M, P < 0.001 vs. oxcarbazepine and monohydroxy derivative). Limitation of firing by oxcarbazepine and the monohydroxy derivative depended on firing frequency and membrane potential and was enhanced by depolarization. Input resistance and resting membrane potential were not altered by either drug. The in vitro effect on action potential firing frequency occurred at concentrations below plasma levels of oxcarbazepine and monohydroxy derivative which protected animals against electroshock and were therapeutically effective in patients.(ABSTRACT TRUNCATED AT 250 WORDS)