Modulatory effects of nifedipine and nimodipine in experimental convulsions

Objectives : To investigate the effect of nifedipine and nimodipine on acute [maximal electroshock and pentylenetetrazol (PTZ) induced convulsions in rats] and chronic (pentylenetetrazol induced kindling in rats and mice) models of epilepsy. Methods: The maximal seizure pattern was induced in animals by giving an alternating current of 150 mA for 0.2 secs, while tonic clonic seizures were seen with 50 mg/kg i.p. dose of PTZ. Test drugs were administered 30 min before electrical or chemical induction. The ability of test drug to abolish/reduce tonic hind limb extensor component in MES group and jerky movements and clonic seizures in PTZ group was selected as antiepileptic criteria. Kindling was established in mice with PTZ in subconvulsive dose (30 mg/kg i.p.) thrice a week for nine weeks and effect observed for 15 min using 4 point scoring system. Rechallenge with same dose on 3rd and 10th day showed that kindling was established. Calcium channel blockers were then administered prior to convulsions and effects observed. Results : In acute studies, both nifedipine and nimodipine decreased the duration of tonic hind limb extensor phase in maximal electroshock seizures while in PTZ (50 mg/kg) treated animals, both drugs significantly decreased the duration of clonic convulsions, only nifedipine increased the latent period while nimodipine did not affect the latent period. The protective effect with nifedipine was significant (p<0.05) at 10 mg/kg while with nimodipine at 5 mg/kg dose. In chronic studies, nifedipine (2 mg/kg) given prophylactically in PTZ (30 mg/kg thrice weekly for 9 weeks) kindled rats and mice significantly (p<0.05) reduced the convulsive score in both the animals, however, the pattern of response was different. No significant effect on kindling was observed with nimodipine. Conclusions :The results with acute studies suggest that both nifedipine and nimodipine, the calcium channel blockers, possess anticonvulsant activity. Chronic studies showed anticonvulsant profile only with nifedipine and better response observed in mice as compared to rats.