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 refract...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.展开更多
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+4 种基金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).
文摘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.
