Epilepsy is a common neurological disorder that is primarily treated with antiseizure medications (ASMs). Although dozens of ASMs are available in the clinic, approximately 30% of epileptic patients have medically refractory seizures; other limitations in most traditional ASMs include poor tolerability and drug-drug interactions. Therefore, there is an urgent need to develop alternative ASMs. Levetiracetam (LEV) is a first-line ASM that is well tolerated, has promising efficacy, and has little drug-drug interaction. Although it is widely accepted that LEV acts through a unique therapeutic target synaptic vesicle protein (SV) 2A, the molecular basis of its action remains unknown. Even so, the next-generation SV2A ligands against epilepsy based on the structure of LEV have achieved clinical success. This review highlights the research and development (R&D) process of LEV and its analogs, brivaracetam and padsevonil, to provide ideas and experience for the R&D of novel ASMs.

癫痫是一种常见的神经系统疾病，主要通过抗癫痫药物 (ASM) 进行治疗。尽管临床上有数十种 ASM，但大约 30% 的癫痫患者患有医学上难治性癫痫发作；大多数传统 ASM 的其他局限性包括耐受性差和药物间相互作用。因此，迫切需要开发替代的ASM。左乙拉西坦 (LEV) 是一线 ASM，耐受性良好，疗效良好，且药物间相互作用很少。尽管人们普遍认为 LEV 通过独特的治疗靶标突触小泡蛋白 (SV) 2A 发挥作用，但其作用的分子基础仍然未知。即便如此，基于LEV结构的下一代抗癫痫SV2A配体已经取得了临床成功。本文重点介绍了LEV及其类似物布瓦西坦和帕地维尼的研发过程，为新型ASM的研发提供思路和经验。