Mechanisms of action of Antiseizure Drugs and the Ketogenic diet

Michael A Rogawski, Wolfgang Löscher, Jong M. Rho

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement of γ-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and α2δ; or by blockade of ionotropic glutamate receptors, including a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, such as adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion fromglycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures.

Original languageEnglish (US)
Article numbera022780
Pages (from-to)28
Number of pages1
JournalCold Spring Harbor perspectives in medicine
Volume6
Issue number5
DOIs
StatePublished - May 1 2016

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Ketogenic Diet
Nutrition
GABA Plasma Membrane Transport Proteins
Seizures
Ion Channels
Pharmaceutical Preparations
gamma-Aminobutyric Acid
Brain
4-Aminobutyrate Transaminase
Aminobutyrates
Isoxazoles
Ionotropic Glutamate Receptors
Drug therapy
AMPA Receptors
Sodium Channels
Synaptic Vesicles
Potassium Channels
Propionates
GABA-A Receptors
Calcium Channels

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mechanisms of action of Antiseizure Drugs and the Ketogenic diet. / Rogawski, Michael A; Löscher, Wolfgang; Rho, Jong M.

In: Cold Spring Harbor perspectives in medicine, Vol. 6, No. 5, a022780, 01.05.2016, p. 28.

Research output: Contribution to journalArticle

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