ArticleEpilepsia2020
A multiorganism pipeline for antiseizure drug discovery: Identification of chlorothymol as a novel γ-aminobutyric acidergic anticonvulsant.
Article in Epilepsia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- SVHRSP Attenuates PTZ-Induced Seizure-Like Behavior in C. elegans: Involvement of HSF-1 and Associated Changes in GABAergic Markers and Mitochondrial Homeostasis.Neurochemical research · 2026Article
- Personalized Drug Repurposing Screen Identifies Patient-Specific Therapeutic Candidates for Mucopolysaccharidosis Type IIIB.Journal of personalized medicine · 2026Article
- Article
- Alzheimer's disease-associated genotypes differentially influence chronic evoked seizure outcomes and antiseizure medicine efficacy in aged mice.Journal of Alzheimer's disease : JAD · 2025Article
- Automated detection of complex zebrafish seizure behavior at scale.Communications biology · 2025Article
- Innovative drug discovery strategies in epilepsy: integrating next-generation syndrome-specific mouse models to address pharmacoresistance and epileptogenesis.Expert opinion on drug discovery · 2024Review
- Functional analysis of epilepsy-associated GABAEpilepsia open · 2024Article
- A screen of pharmacologically active compounds to identify modulators of the Adgrg6/Gpr126 signalling pathway in zebrafish embryos.Basic & clinical pharmacology & toxicology · 2023Article
- A Caenorhabditis elegans model of autosomal dominant adult-onset neuronal ceroid lipofuscinosis identifies ethosuximide as a potential therapeutic.Human molecular genetics · 2023Article
- Aquatic Freshwater Vertebrate Models of Epilepsy Pathology: Past Discoveries and Future Directions for Therapeutic Discovery.International journal of molecular sciences · 2022Review
- Genetic modeling of GNAO1 disorder delineates mechanisms of Gαo dysfunction.Human molecular genetics · 2022Article
- Can Old Animals Reveal New Targets? The Aging and Degenerating Brain as a New Precision Medicine Opportunity for Epilepsy.Frontiers in neurology · 2022Review
- A zebrafish-centric approach to antiepileptic drug development.Disease models & mechanisms · 2021Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
objectiveCurrent medicines are ineffective in approximately one-third of people with epilepsy. Therefore, new antiseizure drugs are urgently needed to address this problem of pharmacoresistance. However, traditional rodent seizure and epilepsy models are poorly suited to high-throughput compound screening. Furthermore, testing in a single species increases the chance that therapeutic compounds act on molecular targets that may not be conserved in humans. To address these issues, we developed a pipeline approach using four different organisms.
methodsWe sequentially employed compound library screening in the zebrafish, Danio rerio, chemical genetics in the worm, Caenorhabditis elegans, electrophysiological analysis in mouse and human brain slices, and preclinical validation in mouse seizure models to identify novel antiseizure drugs and their molecular mechanism of action.
resultsInitially, a library of 1690 compounds was screened in an acute pentylenetetrazol seizure model using D rerio. From this screen, the compound chlorothymol was identified as an effective anticonvulsant not only in fish, but also in worms. A subsequent genetic screen in C elegans revealed the molecular target of chlorothymol to be LGC-37, a worm γ-aminobutyric acid type A (GABA SIGNIFICANCE: These findings establish a multiorganism approach that can identify compounds with evolutionarily conserved molecular targets and translational potential, and so may be useful in drug discovery for epilepsy and possibly other conditions.
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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.