Protective effect of clozapine against pentylenetetrazol convulsions and kindling

The atypical antipsychotic clozapine treatment (at high doses) has been reported to be associated with tremors. However, antitremor effects of clozapine have also been reported in Parkinsonian patients. Recently, we reported the protective effects of acute clozapine against pilocarpine-induced status epilepticus (SE). With this background, this study was designed to investigate the possible protective effect of clozapine against acute chemoconvulsions and kindling seizures produced by pentylenetetrazol (PTZ) in mice. Various doses of clozapine (1.0, 2.5, 5.0 and 7.5 mg) offered different degrees of protective effects against 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 extensor phase and reduced mortality. Animals chronically pretreated with clozapine (2.5, 7.5 and 15.0 mg) for 8 days when challenged by PTZ (50 and 80 mg) on the 8th day also showed protection. Repeated administration 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. Pretreatment with clozapine (1 or 5 mg) prevented the behavioral manifestations (motor seizures) as well as the development of kindling. The effect was compared with GABA (200 mg) and diazepam (1 mg), a known anticonvulsant drug.