Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil.

Autor: Wu PP; Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; University of Chinese Academy of Sciences, Beijing, 100049, China., Cao BR; Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; University of Chinese Academy of Sciences, Beijing, 100049, China., Tian FY; Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. tianfuyun@zidd.ac.cn.; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, 528400, China. tianfuyun@zidd.ac.cn., Gao ZB; Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. zbgao@simm.ac.cn.; University of Chinese Academy of Sciences, Beijing, 100049, China. zbgao@simm.ac.cn.; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, 528400, China. zbgao@simm.ac.cn.
Jazyk: angličtina
Zdroj: Neuroscience bulletin [Neurosci Bull] 2024 May; Vol. 40 (5), pp. 594-608. Date of Electronic Publication: 2023 Oct 28.
DOI: 10.1007/s12264-023-01138-2
Abstrakt: 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.
(© 2023. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)
Databáze: MEDLINE
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