The NMDA antagonist procyclidine, but not ifenprodil, enhances the protective efficacy of common antiepileptics against maximal electroshock-induced seizures in mice

Abstract

Procyclidine (up to 20 mg/kg i.p.) did not influence the electroconvulsive threshold per se, but when given in a dose of 10 mg/kg, it potentiated the protective activity of carbamazepine, diphenylhydantoin, phenobarbital and valproate, and in a dose of 20 mg/kg, that of diazepam against maximal electroshock-induced convulsions in mice. Ifenprodil increased the threshold for electroconvulsions when applied at 20 and 40 mg/kg (i.p.), but surprisingly, when combined with all antiepileptics tested, it did not influence their anticonvulsant actions. The chimney test in mice revealed, that application of procyclidine at 10 mg/kg together with phenobarbital and valproate, and procyclidine at 20 mg/kg with diazepam resulted in motor impairment. However, when procyclidine was applied at 10 mg/kg together with carbamazepine or diphenylhydantoin, no motor impairment was noted. The combined treatment of procyclidine (10 mg/kg) with carbamazepine, diphenylhydantoin, phenobarbital or valproate, as well as procyclidine (20 mg/kg) with diazepam caused significant worsening of long-term memory. Finally, procyclidine did not alter the total plasma levels of carbamazepine, diazepam, diphenylhydantoin, phenobarbital and valproate. It may be concluded that not all agents interfering with NMDA receptor complex-mediated events lead to the potentiation of the anticonvulsant activity of antiepileptic drugs.