A POTENTIAL ANTIASTHMATIC DRUG, CR-2039, ENHANCES THE ANTICONVULSIVE ACTIVITY OF SOME ANTIEPILEPTIC DRUGS AGAINST PENTETRAZOL IN MICE

CR 2039 zol-5-yl)-N-[4-(1H-tetrazol-5-yl]phenylbenzamide), in doses of 10, 20, and 100 mg/kg i.p., did not modify the seizure pattern observ ed after subcutaneous pentetrazol, administered at its CD97 of 90 mg/k g for the clonic phase. However, when combined with antiepileptic drug s, this phenylbenzamide derivative (20 mg/kg) converted the subprotect ive doses of ethosuximide (100 mg/kg) or valproate (100 mg/kg) against the clonic phase into anticonvulsive ones. The protection observed wa s comparable to that noted after doubling the doses of these antiepile ptics. Also, a combination of valproate (100 mg/kg) with CR 2039 (10 m g/kg) resulted in a clear-cut protection against clonic seizures induc ed by pentetrazol. The protective efficacy of clonazepam was not affec ted by the phenylbenzamide derivative up to 40 mg/kg. The potentiation of the anticonvulsive activity of ethosuximide or valproate was not a ccompanied by increased adverse effects, evaluated in the chimney test (motor coordination) and passive avoidance task (long-term memory). F inally, CR 2039 (20 mg/kg) did not alter the plasma levels of the anti epileptic drugs studied, which speaks against a pharmacokinetic mechan ism in the observed results. In conclusion, CR 2039 seems devoid of a hazardous influence of the anti-asthmatic drug, aminophylline, on the anticonvulsive effects of conventional antiepileptics. (C) 1998 Elsevi er Science B.V./ECNP.