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| Clinical data | |
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| Pronunciation | stir"i pen' tol |
| Trade names | Diacomit |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a618069 |
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| Routes of administration | By mouth |
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| ECHA InfoCard | 100.051.329 |
| Chemical and physical data | |
| Formula | C14H18O3 |
| Molar mass | 234.295 g·mol−1 |
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Stiripentol, sold under the brand nameDiacomit, is ananticonvulsant medication used for the treatment ofDravet 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]
In the European Union, stiripentol isindicated 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 withsodium valproate andclobazam for treating children withDravet 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]
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]
Very common (more than 10% of people) adverse effects include loss of appetite, weight loss, insomnia, drowsiness,ataxia,hypotonia, anddystonia.[9]
Common (between 1% and 10% of people) adverse effects includeneutropenia (sometimes severe), aggressiveness, irritability, behavior disorders, opposing behavior, hyperexcitability, sleep disorders, hyperkinesias, nausea, vomiting, and elevatedgamma-glutamyltransferase.[9]
Stiripentol inhibits severalcytochrome P450isoenzymes and so interacts with many anticonvulsants and other medicines.[9]
As with most anticonvulsants, the precise mechanism of action is unknown. Regardless, stiripentol has been shown to have anticonvulsant effects of its own.
Stiripentol increasesGABAergic activity. At clinically relevant concentrations, it enhances central GABA neurotransmission through abarbiturate-like effect, since it increases the duration of opening of GABA-A receptor channels in hippocampal slices.[12] It has also been shown to increaseGABA levels in brain tissues by interfering with its reuptake andmetabolism.[13] Specifically, it has been shown to inhibitlactate 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 ofATP-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 increasingblood plasma levels.[9]
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]
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, theEuropean Medicines Agency (EMA) granted stiripentolorphan drug status (designation number EU/3/01/071) for the treatment ofsevere 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]
In August 2018, stiripentol was approved by the USFood and Drug Administration (FDA) as an adjunctive therapy for Dravet Syndrome.[18]
Prior to approval in the US, parents of children with Dravet Syndrome were paying around $1,000 for a month supply to obtain it from Europe.[19]
