Presynaptic antiseizure medications - basic mechanisms and clues for their rational combinations

Pharmacol Rep. 2024 Aug;76(4):623-643. doi: 10.1007/s43440-024-00603-7. Epub 2024 May 22.

Abstract

Among clinically highly efficient antiseizure medications (ASMs) there are modifiers of the presynaptic release machinery. Of them, levetiracetam and brivaracetam show a high affinity to the synaptic vesicle protein type 2 A (SV2A), whereas pregabalin and gabapentin are selective ligands for the α2δ1 subunits of the voltage-gated calcium channels. In this paper, we present recent progress in understanding the significance of presynaptic release machinery in the neurochemical mechanisms of epilepsy and ASMs. Furthermore, we discuss whether the knowledge of the basic mechanisms of the presynaptically acting ASMs might help establish a rational polytherapy for drug-resistant epilepsy.

Keywords: Antiseizure medications; Clinical efficacy; Epilepsy; Neurochemical mechanisms; Presynaptic machinery; Rational polytherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticonvulsants* / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Epilepsy / drug therapy
  • Epilepsy / metabolism
  • Humans
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism

Substances

  • Anticonvulsants
  • Calcium Channels