ANTIEPILEPTIC EFFECT OF CALCIUM CHANNEL BLOCKERS ALONE AND IN COMBINATION WITH PHENYTOIN ON MES INDUCED EPILEPSY IN RATS

Abstract

Background: The currently available antiepileptic drugs have a low therapeutic index, and provide satisfactory seizure control in only 60-70% of patients. Calcium channel blocker has shown potentials of a useful add-on drug for the existing antiepileptic drugs. Objectives: To study the effect of calcium channel blockers (CCBs) nifedipine and verapamil on maximal electroshock (MES)-induced convulsions and also to evaluate their effect in combination with Phenytoin. Methods: For this study, Male Wistar rats were used. Effects of nifedipine (5 mg/kg), verapamil (20mg/kg) alone and in combination with phenytoin (25mg/kg) were studied in MES model. Abolition of hind limb tonic extension and reduction of duration of tonic extension was considered as the index for antiepileptic activity in MES. Results: Verapamil and nifedipine produced significant antiepileptic effect alone. Verapamil and nifedipine potentiated the antiepileptic effect of phenytoin sodium. Conclusion: Dose of phenytoin sodium can be reduced in epileptic patients receiving verapamil or nifedipine for some other clinical conditions. Verapamil and nifedipine can also be used alone in the treatment of generalized tonic clonic seizures. However it needs further confirmation to establish clinical utility of calcium channel blockers.

KEY WORDS: Nifedipine, verapamil, phenytoin, MES seizure rats.