Comparative evaluation of anticonvulsant activity of calcium channel blockers in experimental animals.

Pentylenetetrazole (PTZ)-induced convulsions and the maximal electroshock (MES) seizure test were employed to study the anticonvulsant effects of nifedipine (2, 3.5 and 5 mg kg-1), flunarizine (10, 20 and 40 mg kg-1) and diltiazem (10, 15 and 30 mg kg-1). Nifedipine and flunarizine prolonged the latent period and reduced the mean duration of PTZ induced seizures. They also reduced the severity of convulsions and the number of deaths due to PTZ significantly. Nifedipine was more potent in this regard (P < 0.01). All these drugs prolonged the latent period and reduced the duration of tonic extensor phase of MES seizures in a significant manner. Flunarizine was most potent in this test. Complete protection from tonic extensor phase was observed in 10-50% animals pretreated with nifedipine and flunarizine in a dose dependent manner. The response of diltiazem was weak in both these tests. It is concluded that all three calcium channel blockers possess an important but different anticonvulsant effect and their significant clinical use can be made while keeping in view the characteristics of their pharmacological action.

Effect of nifedipine, a calcium channel inhibitor, on sedation produced by reserpine, clonidine and propranolol in mice.

Spontaneous motor activity, rotarod test and observational rating of sedation were employed to study effect of nifedipine on sedation produced by reserpine, clonidine and propranolol. Reserpine (2 mg kg-1), clonidine (4 mg kg-1), and propranolol (40 mg kg-1) significantly reduced spontaneous motor activity and staying capacity of animals on accelerating rotarod (P < 0.01). Observational sedation was also caused significantly as indicated by a higher score in test. Nifedipine (2 mg kg-1) produced no sedation or excitation on its own. Reduction in spontaneous motor activity produced by reserpine and clonidine was partially reversed in animals treated with nifedipine (P < 0.01). A similar effect of nifedipine was also evident on the observational sedation induced by reserpine and clonidine. Effect of these drugs on rotarod times was nearly totally antagonised by nifedipine. Nifedipine did not oppose the sedation produced by propranolol which actually became significantly greater in the animals pretreated with nifedipine in all three tests. It is concluded that nifedipine antagonizes the sedation produced by reserpine and clonidine, probably by blocking central alpha 2-adrenoceptors. The sedative effect of propranolol can be potentiated by nifedipine possibly because of a pharmacokinetic interaction.