PDF(Pubmed)
Abstract：
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.
摘要：
癫痫是一种常见的神经系统疾病，主要用抗癫痫药物（ASM）治疗。虽然诊所里有几十个ASM，大约30%的癫痫患者有药物难治性癫痫发作;大多数传统ASM的其他限制包括耐受性差和药物-药物相互作用.因此,左乙拉西坦（LEV）是一线ASM，耐受性良好，有很好的疗效，几乎没有药物-药物相互作用。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起作用，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配体已取得临床成功.本文重点介绍了LEV及其类似物的研发(R&D)过程,brivaracetam和padsevonil,为新型ASM的研发提供思路和经验。
