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

作　　者：Peng-Peng Wu Bi-Rong Cao Fu-Yun Tian Zhao-Bing Gao 

机构地区：[1]Center for Neurological and Psychiatric Research and Drug Discovery,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [2]University of Chinese Academy of Sciences,Beijing,100049,China [3]Zhongshan Institute for Drug Discovery,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Zhongshan,528400,China

出　　处：《Neuroscience Bulletin》2024年第5期594-608,共15页神经科学通报（英文版）

基　　金：supported by funding from the High-level New R&D Institute(2019B090904008);the High-level Innovative Research Institute(2021B0909050003)of the Department of Science and Technology of Guangdong Province;National Science and Technology Innovation 2030 Major Program(2021ZD0200900);Shanghai Municipal Science and Technology Major Project(2018SHZDZX05);Zhongshan Municipal Bureau of Science and Technology(CXTD2022013);the National Science Fund for Distinguished Young Scholars(81825021);the funding from Zhongshan Municipal Bureau of Science and Technology(210724194041939).

摘　　要：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.

关 键 词：LEVETIRACETAM EPILEPSY Antiseizure medications Synaptic vesicle protein 2A BRIVARACETAM Padsevonil 

分 类 号：R741[医药卫生—神经病学与精神病学]