J Neural Transm (1996) 103:1371-1379 __Journal of_ Neural Transmission 9 Springer-Verlag 1996 Printed in Austria Influence of a potential anti-asthmatic drug, CR 2039, upon the anticonvulsive activity of conventional antiepileptics against maximal electroshock-induced seizures in mice S. J. Czuczwar, M. Gasior, M. Kozicka, T. Pietrasiewicz, W. A. Turski, and Z. Kleinrok Department of Pharmacology, Lublin Medical University School, Lublin, Poland Accepted August 20, 1996 Summary. CR 2039 [4-(1H-tetrazol-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 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 10mg/ kg) potentiated the anticonvulsive action of these antiepileptics against maxi- mal electroshock-induced convulsions which was reflected by significant de- creases in the respective EDs0s (in mg/kg). The protective efficacy of phenobarbital was not affected by the phenylbenzamide derivative. The po- tentiation of the anticonvulsive activity of three antiepileptics was not accom- panied by increased adverse effects, evaluated in the chimney test (motor coordination) and passive avoidance task (long-term memory). Finally, CR 2039 (10mg/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 chroni- cally, considerably impaired the anticonvulsive activity of conventional antiepileptics. Keywords: Antiepileptics, CR 2039, seizures. Introduction Theophylline is a methylxanthine derivative possessing a bronchodilatory activity. Its importance has recently declined for asthma therapy (Serafin, 1996). Nevertheless, theophylline, administered usually in the form of aminophylline (theophylline2ethylenediamine), is still prescribed for the treatment of asthma and status asthmaticus (Ukena and Sybrecht, 1990).