DRAVET SYNDROME

The effects of stiripentol on GABAA receptors

  1. Janet L. Fisher

Article first published online: 4 APR 2011

DOI: 10.1111/j.1528-1167.2011.03008.x

Issue

Epilepsia

Epilepsia

Special Issue: Severe Myoclonic Epilepsy – Dravet Syndrome: Thirty Years Later

Volume 52, Issue Supplement s2, pages 76–78, April 2011

Additional Information

How to Cite

Fisher, J. L. (2011), The effects of stiripentol on GABAA receptors. Epilepsia, 52: 76–78. doi: 10.1111/j.1528-1167.2011.03008.x

Author Information

  1. Department of Pharmacology, Physiology and Neuroscience, School of Medicine, University of South Carolina, Columbia, South Carolina, U.S.A.

*Author correspondence to Janet L. Fisher, Department of Pharmacology, Physiology and Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208, U.S.A. E-mail: jfisher@uscmed.sc.edu

Publication History

  1. Issue published online: 4 APR 2011
  2. Article first published online: 4 APR 2011

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Keywords:

  • Recombinant;
  • Patch-clamp;
  • Dravet syndrome

Summary

The anticonvulsant stiripentol (Diacomit™) has been shown to have a positive impact on control of seizures for many patients with Dravet syndrome. As with most antiepileptic drugs, stiripentol has multiple mechanisms of action. Its direct anticonvulsant activity is likely due to enhancement of inhibitory, γ-aminobutyric acid (GABA)ergic neurotransmission. Stiripentol was shown to increase the activity of both neuronal and recombinant GABAA receptors at clinically relevant concentrations. At recombinant receptors, stiripentol was found to act through a unique site in a subunit-dependent manner. Positive modulation by stiripentol was most effective at GABAA receptors containing an α3 subunit. The expression of the α3 subunit is developmentally regulated, with highest levels in the immature brain. This subunit selectivity may explain the greater clinical efficacy of stiripentol in childhood-onset epilepsies, including Dravet syndrome.

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