Department of Neurology, Joint Research Institution of Altitude Health, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
J Med Chem. 2023 Apr 13;66(7):4434-4467. doi: 10.1021/acs.jmedchem.2c01975. Epub 2023 Apr 3.
Epilepsy is a common disease of the nervous system characterized by transient brain dysfunction caused by an abnormal electrical discharge from the brain neurons. The pathogenesis of epilepsy is complex and remains elusive. Nowadays, drug therapy is the mainstay method for the treatment of epilepsy. More than 30 antiseizure drugs (ASDs) were approved for clinical use. Unfortunately, about 30% of patients still display pharmacoresistance against ASDs. The long-term use of ASDs may cause adverse effects, raise tolerability concerns, bring unexpected drug interactions, generate withdrawal symptoms, and increase the economic burden. Thus, the research uncovering more effective ASDs that are safe is still a difficult and urgent task. In this Perspective, we describe the pathogenesis, clinical trials, and drug therapy progress of epilepsy, focusing on summarizing the current situation of small-molecule drug candidates progressing in epilepsy therapy, which provides future directions for the development of more promising ASDs.
癫痫是一种常见的神经系统疾病,其特征是由于大脑神经元异常放电导致短暂的大脑功能障碍。癫痫的发病机制复杂,至今仍难以捉摸。目前,药物治疗是治疗癫痫的主要方法。已有超过 30 种抗癫痫药物(ASD)获准用于临床。不幸的是,约 30%的患者对 ASD 仍存在耐药性。ASD 的长期使用可能会引起不良反应,引起耐受性问题,产生意想不到的药物相互作用,产生戒断症状,并增加经济负担。因此,寻找更有效且安全的 ASD 仍然是一项艰巨而紧迫的任务。在本文观点中,我们描述了癫痫的发病机制、临床试验和药物治疗进展,重点总结了目前在癫痫治疗中进展的小分子药物候选物的现状,为开发更有前途的 ASD 提供了未来的方向。