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Stiripentol
Clinical data
Pronunciation	stir"i pen' tol
Trade names	Diacomit
AHFS/Drugs.com	Monograph
MedlinePlus	a618069
License data	US DailyMed: Stiripentol;
Pregnancy; category	AU: B3; ;
Routes of; administration	By mouth
ATC code	N03AX17 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only; EU: Rx-only; In general: ℞ (Prescription only);
Identifiers
	IUPAC name (RS)-(E)-4,4-dimethyl-1-[3,4(methylenedioxy)-phenyl]-1-penten-3-ol;
CAS Number	137767-55-6 ;
PubChem CID	5311454;
IUPHAR/BPS	5469;
DrugBank	DB09118 ;
ChemSpider	4470940 ;
UNII	R02XOT8V8I;
KEGG	D05928 ;
ChEMBL	ChEMBL1983350;
CompTox Dashboard (EPA)	DTXSID80860609 DTXSID6049068, DTXSID80860609 ;
ECHA InfoCard	100.051.329
Chemical and physical data
Formula	C14H18O3
Molar mass	234.295 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O1c2ccc(cc2OC1)/C=C/C(O)C(C)(C)C;
	InChI InChI=1S/C14H18O3/c1-14(2,3)13(15)7-5-10-4-6-11-12(8-10)17-9-16-11/h4-8,13,15H,9H2,1-3H3/b7-5+ ; Key:IBLNKMRFIPWSOY-FNORWQNLSA-N ;
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Stiripentol, sold under the brand name Diacomit, is an anticonvulsant medication used for the treatment of Dravet syndrome - a serious genetic brain disorder.^[5]^[6]

The most common side effects include loss of appetite, weight loss, insomnia (difficulty sleeping), drowsiness, ataxia (inability to co‑ordinate muscle movements), hypotonia (low muscle strength) and dystonia (muscle disorders).^[5]

Medical uses

In the European Union, stiripentol is indicated for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in people with severe myoclonic epilepsy in infancy (SMEI, Dravet's syndrome) whose seizures are not adequately controlled with clobazam and valproate.^[5]

In the United States, stiripentol is indicated for the treatment of seizures associated with Dravet syndrome in people two years of age and older taking clobazam.^[4] There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome.^[4]

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.^[7]^[8]^[9]^[10] As of 2017, it was not known whether stiripentol remains useful as children become adolescents or adults.^[11]

Contraindications

Stiripentol must not be used in people who have had psychosis (a serious mental state with a distorted sense of reality) with attacks of delirium (a mental state with confusion, excitement, restlessness and hallucinations).^[5]

Adverse effects

Very common (more than 10% of people) adverse effects include loss of appetite, weight loss, insomnia, drowsiness, ataxia, hypotonia, and dystonia.^[9]

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.^[9]

Interactions

Stiripentol inhibits several cytochrome P450 isoenzymes and so interacts with many anticonvulsants and other medicines.^[9]

Pharmacology

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.^[12] It has also been shown to increase GABA levels in brain tissues by interfering with its reuptake and metabolism.^[13] 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.^[14]

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.^[9]

Chemistry

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 used medically as the racemate. The R enantiomer appears to be around 2.5 times more active than the S enantiomer.^[15]

History

Stiripentol was discovered in 1978 by scientists at Biocodex and clinical trials started over the next few years.^[15] It was originally developed for adults with focal seizures, but failed a Phase III trial.^[11]

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 January 2007, the EMA granted the drug a marketing authorisation for use of the drug as an add-on to other anti-seizure drugs.^[5]^[9] It was approved in Canada for this use in May 2013.^[16]^[17] As of 2017, it was also approved for this use in Japan.^[8]