|AHFS/Drugs.com||International Drug Names|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||234.295 g·mol−1|
|3D model (JSmol)|
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Stiripentol (marketed as Diacomit by Laboratoires Biocodex) is an anticonvulsant drug used in the treatment of epilepsy. It is approved for the treatment of Dravet syndrome, an epilepsy syndrome. It is unrelated to other anticonvulsants and belongs to the group of aromatic allylic alcohols.
It is used in some countries as an add-on therapy with sodium valproate and clobazam for treating children with Dravet syndrome whose seizures are not adequately controlled. As of 2017 it was not known whether stiripentol remains useful as children become adolescents nor as they become adults.
Common (between 1% and 10% of people) adverse effects include neutropenia (sometimes severe), aggressiveness, irritability, behavior disorders, opposing behavior, hyperexcitability, sleep disorders, hyperkinesias, nausea, vomiting, and elevated gamma-glutamyltransferase.
As with most anticonvulsants, the precise mechanism of action is unknown. Regardless, stiripentol has been shown to have anticonvulsant effects of its own.
Stiripentol increases GABAergic activity. At clinically relevant concentrations, it enhances central GABA neurotransmission through a barbiturate-like effect, since it increases the duration of opening of GABA-A receptor channels in hippocampal slices. It has also been shown to increase GABA levels in brain tissues by interfering with its reuptake and metabolism. Specifically, it has been shown to inhibit lactate dehydrogenase, which is an important enzyme involved in the energy metabolism of neurons. Inhibition of this enzyme can make neurons less prone to fire action potentials, likely through activation of ATP-sensitive potassium channels.
Stiripentol is an α-ethylene alcohol; its chemical formula is 4,4-dimethyl-1-[3,4-(methylendioxy)-phenyl]-1penten-3-ol. It is chiral and is marketed as an equimolar racemic mixture. The R enantiomer appears to be around 2.5 times more active than the S enantiomer.
Stiripentol was discovered in 1978 by scientists at Biocodex and clinical trials started over the next few years. It was originally developed for adults with focal seizures, but failed a Phase III trial.
In December 2001 the European Medicines Agency (EMA) granted stiripentol orphan drug status (designation number EU/3/01/071) for the treatment of severe myoclonic epilepsy of infancy (SMEI, also known as Dravet's syndrome) in children and in 2007, the EMA granted the drug a marketing authorisation for use of the drug as an add-on to other anti-seizure drugs. It was approved in Canada for this use in 2012. As of 2017 it was also approved for this use in Japan.
In 2018, stiripentol was approved by the United States Food & Drug Administration as an adjunctive therapy for Dravet Syndrome. Prior to approval, parents of children with Dravet were paying around $1,000 for a month supply to obtain it from Europe.
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- Sada N, Lee S, Katsu T, Otsuki T, Inoue T (2015). "Targeting LDH enzymes with a stiripentol analog to treat epilepsy". Science. 347 (6228): 1362–67. doi:10.1126/science.aaa1299. PMID 25792327.
- "Scientific evaluation" (PDF). EMA. 2007.
- "Stiripentol (Diacomit): For Severe Myoclonic Epilepsy in Infancy (Dravet Syndrome)" (PDF). Canadian Agency for Drugs and Technologies in Health. April 2015.
- "Diacomit website". Diacomit. Retrieved 2020-06-29.
- Kossoff, E (January 2014). "Stiripentol for dravet syndrome: is it worth it?". Epilepsy Currents. 14 (1): 22–3. doi:10.5698/1535-7597-14.1.22. PMC 3913306. PMID 24526870.