PROTECTIVE EFFECT OF CLOZAPINE AGAINST PENTYLENETETRAZOL CONVULSIONS AND KINDLING

The atypical antipsychotic clozapine treatment (at high doses) has bee n reported to be associated with tremors. However, antitremor effects of clozapine have also been reported in Parkinsonian patients. Recentl y we reported the protective effects of acute clozapine against piloca rpine-induced status epilepticus (SE). With this background, this stud y was designed to investigate the possible protective effect of clozap ine against acute chemoconvulsions and kindling seizures produced by p entylenetetrazol (PTZ) in mice. Various doses of clozapine (1.0, 2.5, 5.0 and 7.5 kg) offered different degrees of protective effects agains t PTZ (80 mg) challenge, and the maximum protection was observed with the 2.5 mg dose as it delayed the onset of jerks, clonus, tonic extens or phase and reduced mortality. Animals chronically pretreated with cl ozapine (2.5. 7.5 and 15.0 mg) for 8 days when challenged by PTZ (50 a nd 80 mg) on the 8th day also showed protection. Repeated administrati on of PTZ at a subconvulsive dose (30 mg/kg, i.p, three times a week, for 9 weeks) produced kindled seizures in over 80% of the mice. Pretre atment with clozapine (1 or 5 mg) prevented the behavioral manifestati ons (motor seizures) as well as the development of kindling. The effec t was compared with GABA (200 mg) and diazepam (1 mg), a known anticon vulsant drug. (C) 1998 Prous Science. All rights reserved.