RIMCAZOLE, A SIGMA-RECEPTOR LIGAND, AND THE ANTICONVULSIVE ACTION OF CONVENTIONAL ANTIEPILEPTIC DRUGS

Rimcazole (a selective sigma receptor antagonist) at 5 and 10 mg/kg, 3 0 min before the test, lowered the electroconvulsive threshold, being ineffective at 2.5 mg/kg. Rimcazole (2.5 and 5 mg/kg) enhanced the pro tective activity of phenobarbital and valproate, but not that of carba mazepine and diphenylhydantoin against maximal electroshock. The effec t of rimcazole upon the electroconvulsive threshold was reversed by ha loperidol (0.5 mg/kg), but the rimcazole-induced potentiation of the a nticonvulsive action of antiepileptics was not. Moreover, rimcazole (2 .5 mg/ kg) did not alter the total or free plasma levels of valproate or phenobarbital, so a pharmacokinetic interaction is not probable. Th e combined treatment of rimcazole with antiepileptic drugs, providing a 50% protection against maximal electroshock, did not affect motor pe rformance in mice, although it resulted in significant long-term memor y deficits. Our data indicate that rimcazole, in spite of lowering the seizure threshold, may enhance the protective activity of some antiep ileptic drugs.