ArticleBrain : a journal of neurology2017
Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome.
Article in Brain : a journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 232 citations in OpenAlex.
- Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses and Dose Titration of Bexicaserin in Healthy Participants in a Randomized, Double-Blind, Placebo-Controlled Study.Clinical pharmacology in drug development · 2026Trial
- 5-(Benzofuran-2-yl)-3-(2-chloro-4-fluorobenzyl)-1,3,4-oxadiazol-2(3H)-one (GM-90663) Alleviates Dravet Syndrome via Inhibiting Monoamine Oxidase Activity.Molecules (Basel, Switzerland) · 2026Article
- Whole-brain cellular-resolution functional network properties of seizure susceptibility.bioRxiv : the preprint server for biology · 2026Article
- Ameliorating Seizures in Dravet Syndrome: A Review of Newly Approved and Investigational Drugs, RNA and Gene-Based Therapies.CNS drugs · 2026Review
- Clemizole inhibits CrtN-driven staphyloxanthin biosynthesis in Staphylococcus aureus to enhance host immune clearance.Communications biology · 2026Article
- Zebrafish models of developmental epileptic encephalopathy accurately reflect clinical electrographic biomarkers.Epilepsia · 2026Article
- Employing zebrafish to understand genetic drivers of epilepsy-related comorbid behaviors.Frontiers in pharmacology · 2026Article
- From Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders.International journal of molecular sciences · 2025Review
- Ontology accelerates few-shot learning capability of large language model: A study in extraction of drug efficacy in a rare pediatric epilepsy.International journal of medical informatics · 2025Article
- A multielectrode array reveals therapeutic potential of translocator protein ligands in a zebrafish model of Dravet syndrome.The Journal of pharmacology and experimental therapeutics · 2025Article
- Automated detection of complex zebrafish seizure behavior at scale.Communications biology · 2025Article
- Structural and accessibility studies highlight the differential binding of clemizole to TRPC5 and TRPC6.Journal of biomolecular structure & dynamics · 2025Article
- Spotlight on mechanism of sudden unexpected death in epilepsy in Dravet syndrome.Translational psychiatry · 2025Review
- Review
- Dravet syndrome: novel insights intoFrontiers in neuroscience · 2025Review
- Validating the antiseizure effects of vitexin and related flavone glycosides in zebrafish.Frontiers in pharmacology · 2025Article
- Zebrafish: unraveling genetic complexity through duplicated genes.Development genes and evolution · 2024Review
- Innovative drug discovery strategies in epilepsy: integrating next-generation syndrome-specific mouse models to address pharmacoresistance and epileptogenesis.Expert opinion on drug discovery · 2024Review
- New epilepsy therapies in development.Nature reviews. Drug discovery · 2024Review
- Zebrafish models of candidate human epilepsy-associated genes provide evidence of hyperexcitability.iScience · 2024Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Dravet syndrome is a catastrophic childhood epilepsy with early-onset seizures, delayed language and motor development, sleep disturbances, anxiety-like behaviour, severe cognitive deficit and an increased risk of fatality. It is primarily caused by de novo mutations of the SCN1A gene encoding a neuronal voltage-activated sodium channel. Zebrafish with a mutation in the SCN1A homologue recapitulate spontaneous seizure activity and mimic the convulsive behavioural movements observed in Dravet syndrome. Here, we show that phenotypic screening of drug libraries in zebrafish scn1 mutants rapidly and successfully identifies new therapeutics. We demonstrate that clemizole binds to serotonin receptors and its antiepileptic activity can be mimicked by drugs acting on serotonin signalling pathways e.g. trazodone and lorcaserin. Coincident with these zebrafish findings, we treated five medically intractable Dravet syndrome patients with a clinically-approved serotonin receptor agonist (lorcaserin, Belviq®) and observed some promising results in terms of reductions in seizure frequency and/or severity. Our findings demonstrate a rapid path from preclinical discovery in zebrafish, through target identification, to potential clinical treatments for Dravet syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.