Faculty of Pharmacy, Middle East University, Amman, Jordan.
Eur Rev Med Pharmacol Sci. 2022 Nov;26(22):8534-8538. doi: 10.26355/eurrev_202211_30389.
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.
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.
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.
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.
血脑屏障（BBB）对抗癫痫药物（AEDs）在致痫灶中充分积累的限制被认为是癫痫患者发病率和死亡率高的主要原因。本研究旨在研究胰岛素对苯妥英（PHT）在小鼠最大电休克诱导惊厥模型中的抗惊厥作用的潜在影响。
PHT 单独或与胰岛素联合口服单次给药，胰岛素作为单次腹腔内注射。为了评估 PHT 的抗惊厥活性，计算 ED50 值。还估计了胰岛素的电流强度（CS50）阈值。处死动物，取出大脑，测量大脑中 PHT 的浓度。
结果表明，胰岛素（在所有使用剂量下）对 CS50 没有影响，但可以显著增加 PHT 在大脑中的浓度，并增强这种药物在电休克诱导的癫痫小鼠模型中的抗癫痫作用。
胰岛素与 PHT 的联合应用可能对进一步研究其他癫痫动物模型和临床前研究开发新的治疗可能性具有重要意义。还需要进一步研究以探索糖尿病小鼠大脑中 PHT 的浓度和该药物对最大电休克发作的抗惊厥活性。
