INFLUENCE OF A POTENTIAL ANTIASTHMATIC DRUG, CR-2039, UPON THE ANTICONVULSIVE ACTIVITY OF CONVENTIONAL ANTIEPILEPTICS AGAINST MAXIMAL ELECTROSHOCK-INDUCED SEIZURES IN MICE

CR 2039 ol-5-yl)-N-(4-(1H-tetrazol-5-yl]phenyl-benzamide], in doses of 10, 50, and 100mg/kg i.p., significantly elevated the threshold for e lectroconvulsions, increasing the CS50 (current strength 50% in mA) va lues from 6.3 to 7.2, 7.5, and 7.6 mA, respectively. When combined wit h carbamazepine, diphenylhydantoin, or valproate, CR 2039 (5 and 10 mg /kg) potentiated the anticonvulsive action of these antiepileptics aga inst maximal electroshock-induced convulsions which was reflected by s ignificant decreases in the respective ED(50)s (in mg/kg). The protect ive efficacy of phenobarbital was not affected by the phenylbenzamide derivative. The potentiation of the anticonvulsive activity of three a ntiepileptics was not accompanied by increased adverse effects, evalua ted in the chimney test (motor coordination) and passive avoidance tas k (long-term memory). Finally, CR 2039 (10 mg/kg) did not alter the pl asma levels of the antiepileptic drugs studied which speaks against a pharmacokinetic mechanism in the observed results. It is concluded tha t CR 2039 may prove a safer anti-asthmatic drug for the use in epilept ic patients than aminophylline which, either acutely or chronically, c onsiderably impaired the anticonvulsive activity of conventional antie pileptics.