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Article
Mechanisms of action of antiseizure drugs and the ketogenic diet.
Cold Spring Harb Perspect Med (2016)
  • Michael A. Rogawski
  • Jong M. Rho
  • Wolfgang Löscher
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 gamma-aminobutyric acid (GABA)-mediated inhibition through effects on GABA-A 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 a2d; or by blockade of ionotropic glutamate receptors, including alpha-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 from glycolysis, 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.
Keywords
  • antiseizure drug,
  • antiepileptic drug,
  • ketogenic diet
Publication Date
2016
Citation Information
Michael A. Rogawski, Jong M. Rho and Wolfgang Löscher. "Mechanisms of action of antiseizure drugs and the ketogenic diet." Cold Spring Harb Perspect Med (2016)
Available at: http://works.bepress.com/michael_rogawski/71/