title: The effects of stiripentol on GABA(A) receptors.
abstract: The anticonvulsant stiripentol (Diacomittm) 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 GABA(A) 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 GABA(A) 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.
authors.affiliation: Department of Pharmacology, School of Medicine, University of South Carolina, Columbia, South Carolina 29208, USA. jfisher@uscmed.sc.edu
authors.forename: Janet L
authors.initials: JL
authors.lastname: Fisher
mesh_terms: D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004148:Dioxolanes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004831:Epilepsies, Myoclonic / Q000188:drug therapy* / Q000503:physiopathology; D058785:GABA-A Receptor Agonists / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D011963:Receptors, GABA-A / Q000502:physiology*; D013577:Syndrome
chemical_list: D000927:Anticonvulsants; D004148:Dioxolanes; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; C021092:stiripentol