Evaluation Of Antiepileptic Activities Of Ramipril And Telmisartan And Potentiation Of The Antiepileptic Effect Of Phenytoin Sodium And Valproic Acid In Rat Models

Abstract

Background: Epilepsy is a chronic disorder with heterogeneous symptoms characterized by recurrent seizures resulting from abnormal discharge of cerebral neurons. Several different drugs are available and act through diverse mechanisms. However, most of them have a low safety margin and provide seizure control in 60 - 70% of patients. Attempts are being made to explore the anti-epileptic potentials of several different groups of drugs. Drugs interfering with Renin- Angiotensin- Aldosterone system (RAAS) have shown potential as an add-on therapy with existing anti-epileptic drugs. Objectives: To evaluate the anti-epileptic potential of Ramipril and Telmisartan using the Maximum Electroshock (MES) model and PTZ model in rats and also to evaluate its effect as an add-on with Phenytoin and Sodium Valproate Methods: The study was conducted on Male Wistar rats to investigate the effects of Ramipril (2mg/kg) and Telmisartan (30 mg/kg) individually, as well as in combination with Phenytoin and Sodium Valproate, in models of epilepsy. In the maximal electroshock (MES) model, the rats were administered Ramipril (2mg/kg) and Telmisartan (30 mg/kg) alone and in combination with Phenytoin (Ramipril 1mg/kg + Phenytoin Sodium 50 mg/kg) and (Telmisartan 15 mg/kg + Phenytoin Sodium 50 mg/kg). Phenytoin Sodium (100mg/kg) was used as the standard reference. The effects were assessed based on the abolition of Hind Limb Tonic Extension (HLTE), serving as an index of anti-epileptic activity. Similarly, in the pentylenetetrazole (PTZ) model, the rats received Ramipril (2mg/kg) and Telmisartan (30 mg/kg) alone and in combination with Sodium Valproate (Ramipril 1mg/kg + Sodium Valproate 125 mg/kg) and (Telmisartan 15 mg/kg + Sodium Valproate 125 mg/kg). Sodium Valproate (250mg/kg) was the standard reference. The effects were evaluated based on the delay in the onset of convulsions, another index of anti-epileptic activity. Results: Both Ramipril and Telmisartan exhibited significant anti-epileptic effects when used alone. Both drugs potentiated the anti-epileptic effect of Phenytoin and Sodium Valproate. Conclusion: Drugs interfering with RAS, like Ramipril (ACEI) and Telmisartan (ARB), can be used alone for generalized tonic-clonic convulsions (GTC). In patients receiving ACEIs or ARBs for other clinical conditions, a dose of Phenytoin and Sodium Valproate can be reduced if these patients also have epilepsy.