Mishra Awanish, Goel Rajesh Kumar
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
Basic Clin Pharmacol Toxicol. 2014 Dec;115(6):512-7. doi: 10.1111/bcpt.12275. Epub 2014 Jul 1.
Epilepsy is one of the major neurological disorders still awaiting safer drugs with improved antiepileptic effect and lesser side effects. Apart from epilepsy itself, AEDs also have been shown to induce cognitive impairment in patients with epilepsy. There are limited data for the treatment of this menace. As cholinergic approach has widely been practiced for the restoration of memory in various neurodegenerative disorders, this study was envisaged to evaluate add on effect of acetylcholinesterase inhibitor (tacrine) with phenytoin in pentylenetetrazole-kindling-induced learning and memory deficit in mice. In this study, mice were kindled using subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.; at interval of 48 ± 2 hr) and successfully kindled animals were divided into different groups and treated with vehicle, phenytoin and phenytoinin in combination with tacrine (0.3 mg/kg), atropine (1 mg/kg) and tacrine + atropine. Effect of different interventions on learning and memory was evaluated using elevated plus maze and passive shock avoidance on days 5, 10, 15 and 20. Phenytoin-treated kindled animals were associated with learning and memory deficit, while tacrine supplementation improved memory deficit with increased seizure severity score. Atropine treatment significantly reversed the protective effect of tacrine. Neurochemical findings also support the behavioural finding of the study. Our results suggest the use of anticholinesterases, with better seizure tolerance, for the management of cognitive impairment of epilepsy, as adjunct therapy.
癫痫是主要的神经系统疾病之一，仍在等待具有更好抗癫痫效果和更少副作用的更安全药物。除癫痫本身外，抗癫痫药物还被证明会导致癫痫患者出现认知障碍。针对这种危害的治疗数据有限。由于胆碱能方法已广泛应用于各种神经退行性疾病的记忆恢复，本研究旨在评估乙酰胆碱酯酶抑制剂（他克林）与苯妥英联合应用对戊四氮点燃诱导的小鼠学习和记忆缺陷的附加作用。在本研究中，使用亚惊厥剂量的戊四氮（35毫克/千克，腹腔注射；间隔48±2小时）点燃小鼠，将成功点燃的动物分为不同组，分别用溶剂、苯妥英以及苯妥英与他克林（0.3毫克/千克）、阿托品（1毫克/千克）和他克林+阿托品联合治疗。在第5天、第10天、第15天和第20天，使用高架十字迷宫和被动回避电击试验评估不同干预措施对学习和记忆的影响。接受苯妥英治疗的点燃动物存在学习和记忆缺陷，而补充他克林可改善记忆缺陷，但癫痫严重程度评分增加。阿托品治疗显著逆转了他克林的保护作用。神经化学研究结果也支持该研究的行为学发现。我们的结果表明，作为辅助治疗，使用具有更好癫痫耐受性的抗胆碱酯酶药物来管理癫痫的认知障碍。
