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普瑞巴林与氨氯地平对小鼠癫痫急性发作模型的协同抗惊厥作用。

Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice.

作者信息

Qureshi Itefaq Hussain, Riaz Azra, Khan Rafeeq Alam, Siddiqui Afaq Ahmed

机构信息

Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan.

出版信息

Metab Brain Dis. 2017 Aug;32(4):1051-1060. doi: 10.1007/s11011-017-9979-2. Epub 2017 Mar 9.

Abstract

Status epilepticus is a life threatening neurological medical emergency. It may cause serious damage to the brain and even death in many cases if not treated properly. There is limited choice of drugs for the short term and long term management of status epilepticus and the dugs recommended for status epilepticus possess various side effects. The present study was designed to investigate synergistic anticonvulsant effects of pregabalin with amlodipine on acute seizure model of epilepsy in mice. Pentylenetetrazole was used to induce acute seizures which mimic status epilepticus. Pregabalin and amlodipine were used in combination to evaluate synergistic anti-seizure effects on acute seizure model of epilepsy in mice. Diazepam and valproate were used as reference dugs. The acute anti-convulsive activity of pregabalin with amlodipine was evaluated in vivo by the chemical induced seizures and their anti-seizure effects were compared with pentylenetetrazole, reference drugs and to their individual effects. The anti-seizure effects of tested drugs were recorded in seconds on seizure characteristics such as latency of onset of threshold seizures, rearing and fallings and Hind limbs tonic extensions. The seizure protection and mortality to the animals exhibited by the drugs were recorded in percentage. Combination regimen of pregabalin with amlodipine exhibited dose dependent significant synergistic anticonvulsant effects on acute seizures which were superior to their individual effects and equivalent to reference drugs.

摘要

癫痫持续状态是一种危及生命的神经系统医学急症。如果治疗不当,在许多情况下它可能会对大脑造成严重损害甚至导致死亡。用于癫痫持续状态短期和长期管理的药物选择有限,且推荐用于癫痫持续状态的药物有各种副作用。本研究旨在探讨普瑞巴林与氨氯地平对小鼠癫痫急性发作模型的协同抗惊厥作用。戊四氮用于诱导模拟癫痫持续状态的急性发作。普瑞巴林和氨氯地平联合使用以评估对小鼠癫痫急性发作模型的协同抗癫痫作用。地西泮和丙戊酸盐用作对照药物。通过化学诱导的发作在体内评估普瑞巴林与氨氯地平的急性抗惊厥活性,并将它们的抗癫痫作用与戊四氮、对照药物及其各自的作用进行比较。在几秒钟内记录受试药物对癫痫发作特征的抗癫痫作用,如阈下发作的起始潜伏期、竖毛和跌倒以及后肢强直性伸展。记录药物对动物的癫痫保护作用和死亡率的百分比。普瑞巴林与氨氯地平的联合用药方案对急性发作表现出剂量依赖性的显著协同抗惊厥作用,优于它们各自的作用且等同于对照药物。

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