ArticleEpilepsia2022
Stiripentol inhibits spike-and-wave discharges in animal models of absence seizures: A new mechanism of action involving T-type calcium channels.
Article in Epilepsia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- Efficacy and safety of stiripentol in the prevention and cessation of status epilepticus: A systematic review.Epilepsia open · 2024Pooled it
- Pooled it
- Stiripentol directly attenuates immunosuppression of tumor-infiltrating myeloid cells to potentiate anti-PD-1 efficacy.BMC cancer · 2026Article
- Drug discovery and preclinical testing of drug candidates for developmental and epileptic encephalopathies.Epilepsia · 2025Review
- Efficacy of Stiripentol Beyond Dravet Syndrome: A Retrospective Medical Record Review of Patients with Drug-Resistant Epilepsies.Neurology and therapy · 2025Article
- Voltage-gated calcium channels in genetic epilepsies.Journal of neurochemistry · 2024Review
- Article
- Extrasynaptic δGABAA receptors mediate resistance to migraine-like phenotype in rats.The journal of headache and pain · 2024Article
- An Update on Stiripentol Mechanisms of Action: A Narrative Review.Advances in therapy · 2024Review
- Efficacy and tolerability of add-on stiripentol in real-world clinical practice: An observational study in Dravet syndrome and non-Dravet developmental and epileptic encephalopathies.Epilepsia open · 2024Observational
- New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development.CNS drugs · 2023Review
- Article
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveStiripentol (STP; Diacomit®) is an antiepileptic drug indicated for Dravet syndrome that has been identified as a γ-aminobutyric acid (GABAergic) positive allosteric modulator. Dravet syndrome is characterized by multiple seizure types: generalized tonic-clonic, focal, myoclonic, and absence seizures. In addition to its antiepileptic effects on tonic-clonic seizures, STP has also been reported to reduce the frequency of atypical absence seizures in patients. Our study focused on STP potential effects on absence seizures, to better characterize its full spectrum of mechanisms of action.
methodsSTP effects on absence seizures were quantified by electroencephalographic recording in two animal models: rats treated with a low dose of pentylenetetrazol (20 mg/kg ip) and rats from the WAG/Rij strain. In addition, we characterized STP effects on T-type calcium channel activity. Peak currents were recorded with manual patch clamp on cells transfected with cDNA encoding for the human isoform for Ca
resultsSTP administered before pentylenetetrazol almost completely abolished the generation of spike-and-wave discharges (SWDs) at the dose of 300 mg/kg. At this dose, STP also statistically significantly decreased SWD cumulated duration and number in WAG/Rij rats. Its antiepileptic effect was maintained in WAG/Rij rats, whose seizures were aggravated by the GABA agonist THIP (gaboxadol hydrochloride). Furthermore, electrophysiological recordings showed that STP inhibits T-type calcium channel peak activity, with a higher specificity for the Ca SIGNIFICANCE: In addition to its previously characterized anticonvulsive properties, these data highlight a new mechanism of action of STP on abnormal thalamocortical activity. This strong antiabsence effect on seizures is correlated with an inhibition of T-type calcium channels. This new mechanism of action could be implicated in the specificity of STP therapeutic effects in Dravet syndrome.
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