|Pronunciation||stir"i pen' tol|
|Main uses||Severe myoclonic epilepsy in infancy (Dravet syndrome)|
|Side effects||Loss of appetite, weight loss, trouble sleeping, sleepiness, poor coordination|
|Typical dose||25 mg/kg BID|
|Chemical and physical data|
|Molar mass||234.295 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Stiripentol, sold under the brand name Diacomit, is a medication used to treat a form of epilepsy known as severe myoclonic epilepsy in infancy (SMEI, Dravet syndrome). It is taken by mouth. It is taken with clobazam in children over the age of 2 years.
Common side effects include loss of appetite, weight loss, trouble sleeping, sleepiness, and poor coordination. Other side effects may include low neutrophils, low platelets, and suicide. Use during pregnancy may harm the baby. It is a anticonvulsant with the chemical structure of an aromatic allylic alcohol.
Stiripentol was approved for medical use in Europe in 2007 and the United States in 2018. In the United Kingdom 250 mg twice per day for a month costs the NHS about £280 as of 2021. In the United States this amount costs about 1,600 USD.
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.
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. There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome.
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 or adults.
It is used at a dose of 25 mg/kg twice per day.
Stiripentol must not be used in people who have had psychoses (a serious mental state with a distorted sense of reality) with attacks of delirium (a mental state with confusion, excitement, restlessness and hallucinations).
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 January 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 May 2013. As of 2017, it was also approved for this use in Japan.
Society and culture
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.
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