Insulin potentiates the anticonvulsive activity of phenytoin against maximal electroshock-induced seizures in mice

M. Alaraj, M.J. Saadh, A. Alafnan

Faculty of Pharmacy, Middle East University, Amman, Jordan. m.araj@jpu.edu.jo

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• Pharmacology

INTRODUCTION: The limitations imposed by the blood-brain barrier (BBB) on the sufficient accumulation of antiepileptic drugs (AEDs) in the epileptogenic focus is considered the major cause of the high percentage of morbidity and mortality cases among epilepsy patients. This study aimed at examining the potential effect of insulin on the anticonvulsant action of phenytoin (PHT) in the mouse maximal electroshock-induced seizure model.

SUBJECTS AND METHODS: PHT was administered orally in single doses either alone or in combination with insulin given as single intraperitoneal injections. To assess the anticonvulsant activity of PHT, the ED50 values were calculated. The current strength (CS50) threshold for insulin was also estimated. The animals were sacrificed, and the brains were removed to measure their PHT concentrations in the brain.

RESULTS: It has been demonstrated that insulin (in all used doses) has no effect on the CS50 but can cause a significant increase in concentrations of PHT in the brain and potentiate the antiepileptic efficiency of this drug in electroshock-induced models of epilepsy in mice.

CONCLUSIONS: The combination of insulin with PHT may be of great importance for developing new treatment possibilities following further investigations with other animal models of epilepsy and preclinical studies. Further research is also needed to explore the concentrations of PHT in the brain and the anticonvulsant activity of this drug against maximal electroshock seizures in diabetic mice.

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