Anticonvulsant effect of nifedipine, dizepam and in combination on pentylenetetrazol induced experimental models of epilepsy on albino rats

Abstract

Background: In many patients, the presently available antiepileptic drugs such as phenobarbital, phenytoin, benzodiazepines, sodium valproate, etc., are unable to control seizures efficiently and the problem of adverse effects has also not been circumvented completely and approximately 30% of the patients continue to have seizures with current antiepileptic drugs therapy. Hence, search should continue to develop newer, more effective, and safer neuro-protective agents for treatment of epilepsy. Aim of the study was to investigate the activity of nifedipine, the dihydropyridine calcium channel blocker, diazepam, the benzodiazepine anti- convulsant of established efficacy and their combinations against rat models of pentylenetetrazol (PTZ) induced convulsions. Method: Wister albino rats of either sex, weighing between 150-220gm were used. Rats were divided into 10 groups, in each group n=6 total N=60.Methods: PTZ was administration 30 min after test drug administration. Intraperitoneal injection of PTZ at the dose of 80mg/Kg body weight were administered to the rats to produce chemically-induced seizure. The effect of nifedipine and diazepam were assessed on such seizure model. The onset and duration of clonic convulsion were recorded.Results: The onset time of PTZ-induced clonic convulsion was significantly prolonged with the Nifedipine in the doses of 4mg and 8mg per Kg. in comparison to nifedipine in dose of 2mg per Kg. The interesting observation was that while Diazepam in 1mg/Kg. dose significantly (P<0.05) prolonged the onset time, there was significant decrease (P <0.001) in the onset time of PTZ-induced clonic convulsion with diazepam in doses of 2 and 4mg per Kg. in comparison to Diazepam 1mg per Kg. But the combination of diazepam 2.5 mg and Nifedipine 2.6mg and 5.3mg exhibited significant prolongation of the onset time. Diazepam 1 and 2mg per Kg was found to be equally effective in reduction of convulsion time, while 4mg dose showed more reduction of convulsion time. The combination of diazepam and nifedipine showed no better reduction in the convulsion time and also valproic acid in doses of 135mg. Kg.Conclusions: Nifedipine (3-5mg/Kg) and diazepam (2.5mg/Kg.) combination delayed the onset of convulsion. Diazepam 2mg / Kg. alone was effective in reduction of duration of convulsion. The combination dose having 2.6mg of nifedipine showed comparable protection with valproic acid 135mg per Kg. while the combination having 5.3mg of nifedipine showed significantly better protection.