Stiripentol is an antiepileptic agent used in combination with other anticonvulsants to treat seizures associated with Dravet syndrome. Stiripentol is an antiepileptic agent that is an aromatic allylic alcohol drug, which makes it structurally unique from other antiepileptic drugs. The clinical development and marketing of stiripentol were first delayed due to the drug's potent inhibitory effects on hepatic cytochrome P450 (CYP) enzymes. However, its clinical efficacy as adjunctive therapy for epilepsies stems from its inhibitory action on CYP enzymes, as stiripentol reduces the degradation of CYP-sensitive antiepileptic drugs, hence boosting their therapeutic efficacy. The mechanism by which stiripentol exerts its anticonvulsant effect in humans has not been fully elucidated. Possible mechanisms of action include direct effects mediated through the gamma-aminobutyric acid GABAA receptor and indirect effects involving inhibition of cytochrome P450 activity. Stiripentol also improves the effectiveness of many other anticonvulsants, possibly due to its inhibition of certain enzymes, slowing the drugs' metabolism and increasing blood plasma levels. Stiripentol is a positive allosteric modulator of GABAA receptors in the brain that enhances the opening duration of the channel by binding to a site different than the benzodiazepine binding site. It binds to GABAA receptors containing any of the α, β, γ, or δ-subunits but displays the most potent potency when bound to receptors containing α3 or δ subunits. Stiripentol also binds to GABAA receptor-dependent chloride channels via a barbiturate-like mechanism. Stiripentol potentiates GABA transmission by enhancing the release of GABA, reducing synaptosomal uptake of GABA, and inhibiting GABA transaminase-mediated breakdown of GABA. It can be found under the brand name Diatomite and can cause side effects such as tiredness, shaking, coordination issues, and nausea. Stiripentol is administered as an oral tablet.

Stiripentol GABA(A) Antiepileptic Pathway References