Influence of a potential anti-asthmatic drug, CR 2039, upon the anticonvulsive activity of conventional antiepileptics against maximal electroshock-induced seizures in mice

Abstract

CR 2039 [[4-(1H-tetrazol-5-yl)-N-(4-(1H-tetrazol-5-yl]phenylbenza m ide], in doses of 10, 50, and 100 mg/kg i.p., significantly elevated the threshold for electroconvulsions, increasing the CS50 (current strength 50% in mA) values from 6.3 to 7.2, 7.5, and 7.6 mA, respectively. When combined with carbamazepine, diphenylhydantoin, or valproate, CR 2039 (5 and 10 mg/kg) potentiated the anticonvulsive action of these antiepileptics against maximal electroshock-induced convulsions which was reflected by significant decreases in the respective ED50s (in mg/kg). The protective efficacy of phenobarbital was not affected by the phenylbenzamide derivative. The potentiation of the anticonvulsive activity of three antiepileptics was not accompanied by increased adverse effects, evaluated in the chimney test (motor coordination) and passive avoidance task (long-term memory). Finally, CR 2039 (10 mg/kg) did not alter the plasma levels of the antiepileptic drugs studied which speaks against a pharmacokinetic mechanism in the observed results. It is concluded that CR 2039 may prove a safer anti-asthmatic drug for the use in epileptic patients than aminophylline which, either acutely or chronically, considerably impaired the anticonvulsive activity of conventional antiepileptics.