Dose-Dependent Anticonvulsant and Protective Effects of Metformin in Kainate Induced Temporal Lobe Epilepsy

Abstract

Introduction: Metformin, the most commonly prescribed antidiabetic drug, has been shown to be effective in controlling seizures in some studies. However, there are some reports of proconvulsant activity of metformin in diabetic patients. The aim of the present study was to investigate the effects of metformin dosage on anti-seizure and neuronal protective activity. Method: Male Wistar rats were randomly divided into 5 groups as follows: 1-control/vehicle group, 2Kainic acid (KA), 3-metformin+KA (50 mg/kg), 4-metformin+KA (100 mg/kg), 5metformin+KA (200 mg/ kg). Temporal lobe epilepsy (TLE) was induced by injection of 0.5 μg kainite into the left lateral ventricle. Metformin was administered orally for two weeks before the induction of TLE. Results: We found that metformin at higher doses (100 and 200 mg/ kg) significantly suppressed the progression of seizure in TLE and ameliorated the neuronal loss in the hippocampus induced by KA. However, the low dose of metformin had no effect. Conclusion: We concluded that metformin may be a potential agent for the treatment of epilepsy and seizure and this effect is dose-dependent.