Mechanisms of action of antiseizure drugs

Roger J. Porter, Ashish Dhir, Robert L. Macdonald, Michael A Rogawski

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

This chapter reviews the current understanding of how each of the marketed antiseizure drugs acts on brain mechanisms to protect against seizures. Although the actions of each antiseizure drug have unique characteristics and some drugs may act by multiple mechanisms, the anticonvulsant actions of these drugs can be grouped into four broad categories. These are: (1) modulation of voltage-dependent sodium, calcium or potassium channels; (2) alterations in GABAergic inhibition via actions on GABA A receptors or on GABA synthesis, reuptake, or degradation; (3) decreased synaptic excitation via actions on ionotropic glutamate receptors; and (4) modulation of neurotransmitter release via presynaptic mechanisms. For some antiseizure drugs, the mechanism remains at least partially unknown. An understanding of mechanism may serve as a guide to clinicians as to the seizure types and syndromes that a particular drug may or may not be useful to treat. However, empirical clinical validation is required as the mechanism is not a foolproof predictor of clinical utility. Another use of mechanistic knowledge is to determine rational combinations of drugs for polytherapy. Finally, an understanding of the mechanism may allow the identification of new molecules that act in a mechanistically similar fashion but have improved properties.

Original languageEnglish (US)
Pages (from-to)664-681
Number of pages18
JournalHandbook of Clinical Neurology
Volume108
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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