A new type of anticonvulsant, stiripentol. Pharmacological profile and neurochemical study.
4,4-Dimethyl-1-[3,4-(methylenedioxy)-phenyl]-1-penten-3-ol (stiripentol), selected from a series of alpha-ethylene alcohols, demonstrated anticonvulsant activity in studies in the rat and rabbit in which convulsions were induced electrically and chemically using pentetrazol, bicuculline and strychnine. Neurochemical studies showed that stiripentol in vitro did not act as a GABA receptor agonist, instead it inhibited the synaptosomal uptake of 3H-labelled GABA. Stiripentol has been shown elsewhere to inhibit GABA transaminase. These findings suggest that the anticonvulsant activity of stiripentol involves two aspects of the GABAergic mechanism in which the metabolic transamination and synaptosomal uptake of this neurotransmitter are inhibited.
D000818:Animals; D000927:Anticonvulsants; D001923:Brain Chemistry / Q000187:drug effects*; D004148:Dioxolanes / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D004149:Dioxoles / Q000494:pharmacology*; D004597:Electroshock; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D004148:Dioxolanes; D004149:Dioxoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D005680:gamma-Aminobutyric Acid; C021092:stiripentol