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

Neurosci Bull. 2024 May;40(5):594-608. doi: 10.1007/s12264-023-01138-2. Epub 2023 Oct 28.

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.

Keywords: Antiseizure medications; Brivaracetam; Epilepsy; Levetiracetam; Padsevonil; Synaptic vesicle protein 2A.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticonvulsants* / therapeutic use
  • Epilepsy* / drug therapy
  • Humans
  • Levetiracetam* / therapeutic use
  • Ligands
  • Membrane Glycoproteins / metabolism
  • Nerve Tissue Proteins* / metabolism
  • Pyrrolidinones* / therapeutic use

Substances

  • brivaracetam
  • Levetiracetam
  • Anticonvulsants
  • Pyrrolidinones
  • SV2A protein, human
  • Nerve Tissue Proteins
  • Membrane Glycoproteins
  • Ligands