Evaluation of anticonvulsant activity of ACE inhibitors (imidapril and quinapril) in experimentally induced animal models of epilepsy

Abstract

INTRODUCTIONEpilepsy is a chronic neurological disorder characterized by an enduring predisposition to generate seizures, may be associated with emotional and cognitive dysfunction. This disorder affects 50 million people worldwide and hence, is one of the most common neurological disorder. Despite the availability of a wide range of antiepileptic drugs (AEDs), about one-third of individuals with epilepsy still experience seizures that do not respond to medication.2 Thus, an urgent need exist for effective therapies to be developed. In spite of the vast number of drugs introduced for the treatment of epilepsy, there is still a need for an ideal antiepileptic agent with broad spectrum of activity, rapid onset of action, more economical and least side effects.Epilepsy may be associated with other comorbid conditions like hypertension, diabetes, renal disorders etc. Many researches are in progress, to prove if the drugs used for these disorders like ACE inhibitors, calcium channel blockers, AT II receptor antagonist etc. have any effect on seizure prevention. ABSTRACTBackground: Epilepsy is a chronic neurological disorder characterized by an enduring predisposition to generate seizures, may be associated with emotional and cognitive dysfunction. Objective of this study was to evaluate and compare the anticonvulsant activity of different doses of imidapril and quinapril in animal models of epilepsy. Methods: Swiss albino mice weighing around 25-30g of either sex were divided into 6 groups: control (R.O-10 ml/kg), standard-sodium valproate (40 mg/kg), Q1-quinapril (1.5 mg/kg), Q2-quinapril (10.4 mg/kg), I1-imidapril (0.65mg/kg) and I2-imidapril (2.6 mg/kg). 1 hour after administration of control, test and standard drugs (orally) test was conducted. Convulsions were induced by administering PTZ (70 mg/kg-i.p.) in PTZ model. Seizure latency was the parameter recorded. In MES model, maximal seizures were evoked by supra maximal electroshock stimulation of 50 mA, 50 HZ for 0.2 seconds by using conventional electro convulsion meter. Suppression of tonic hind limb extension was taken as measure of efficacy. Results: The results were analysed by one-way-ANOVA followed by Bonferroni's multiple comparison test. In MES test, dose dependently quinapril and imidapril significantly reduced the duration of tonic hind limb extension in comparison to control (p<0.05) percentage inhibition of seizures by I2 is 58.1%, I1-38.6%, Q2-19.7% and Q1-12.2% with maximum inhibition of seizure produced by I2 in comparison to control in MES test. In PTZ test, dose dependently quinapril and imidapril produced significant increase in seizure latency (p<0.05). Percentage inhibition of seizures by I2-65.8%, I1-59.3%, Q2-50.9% and Q1-33.5% in comparison to control. Conclusions: Quinapril and imidapril in a dose dependent manner showed increase in antiepileptic activity, imidapril has better antiepileptic activity when compared to quinapril.