Role of cinnarizine and nifedipine on anticonvulsant effect of sodium valproate and carbamazepine in maximal electroshock and pentylenetetrazole model of seizures in mice

Objective: To study the effect of calcium channel blockers (CCBs) cinnarizine and nifedipine on maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-induced convulsions and also their effect in combination with conventional antiepileptic drugs (CAED). Materials and Methods: For this study, Swiss albino mice were used. Effects of cinnarizine (30 mg/kg), nifedipine (5 mg/kg), sodium valproate (300 mg/kg) and carbamazepine (8 mg/kg) alone and in combination were studied in MES and PTZ seizure models. Abolition of hind limb tonic extension was an index of anticonvulsant activity in MES, while for PTZ seizures, failure to observe even a single episode of tonic spasm for 5 s duration for 1 h was the index. With this, percentage protection was calculated and statistical analysis was carried out using Fisher's exact test (Ovvind Langsrud software, German version). Results: In MES seizures, augmented effects were obtained when cinnarizine was combined with sodium valproate, i.e. 100%. In PTZ-induced seizures, augmented effects were obtained when nifedipine was combined with sodium valproate, i.e. 100%. Thus, cinnarizine added to sodium valproate therapy produces significant protection against MES seizures while nifedipine added to sodium valproate therapy produces significant protection against PTZ seizures. Conclusion: The results provide a lead for potential benefit of adding CCBs to sodium valproate in the treatment of epilepsy, which needs to be explored further.