ArticleEpilepsia open2021
The opioid antagonist naltrexone decreases seizure-like activity in genetic and chemically induced epilepsy models.
Article in Epilepsia open, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Recurrent neonatal seizures increase tonic inhibition and respond to enhancers of δ-containing GABAA receptors.JCI insight · 2025Article
- Ergolide Regulates Microglial Activation and Inflammatory-Mediated Dysfunction: A Role for the Cysteinyl Leukotriene Pathway.International journal of molecular sciences · 2025Article
- Naltrexone Alters Neurochemical and Behavioral Parameters in a Zebrafish Model of Repeated Alcohol Exposure.Neurochemical research · 2025Article
- Susceptibility to Pentylenetetrazole-Induced Seizures in Mice with Distinct Activity of the Endogenous Opioid System.International journal of molecular sciences · 2024Article
- Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures.Scientific reports · 2024Article
- Enhancing GABAergic Tonic Inhibition Reduces Seizure-Like Activity in the Neonatal Mouse Hippocampus and Neocortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- Article
- Clemizole and trazodone are effective antiseizure treatments in a zebrafish model of STXBP1 disorder.Epilepsia open · 2022Article
- Commentary on "Antiseizure activity by opioid receptor antagonism, new evidence".Epilepsia open · 2022Article
- The opioid antagonist naltrexone decreases seizure-like activity in genetic and chemically induced epilepsy models.Epilepsia open · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveA significant number of epileptic patients fail to respond to available anticonvulsive medications. To find new anticonvulsive medications, we evaluated FDA-approved drugs not known to be anticonvulsants. Using zebrafish larvae as an initial model system, we found that the opioid antagonist naltrexone exhibited an anticonvulsant effect. We validated this effect in three other epilepsy models and present naltrexone as a promising anticonvulsive candidate.
methodsCandidate anticonvulsant drugs, determined by our prior transcriptomics analysis of hippocampal tissue, were evaluated in a larval zebrafish model of human Dravet syndrome (scn1Lab mutants), in wild-type zebrafish larvae treated with the pro-convulsant drug pentylenetetrazole (PTZ), in wild-type C57bl/6J acute brain slices exposed to PTZ, and in wild-type mice treated with PTZ in vivo. Abnormal locomotion was determined behaviorally in zebrafish and mice and by field potential in neocortex layer IV/V and CA1 stratum pyramidale in the hippocampus.
resultsThe opioid antagonist naltrexone decreased abnormal locomotion in the larval zebrafish model of human Dravet syndrome (scn1Lab mutants) and wild-type larvae treated with the pro-convulsant drug PTZ. Naltrexone also decreased seizure-like events in acute brain slices of wild-type mice, and the duration and number of seizures in adult mice injected with PTZ. SIGNIFICANCE: Our data reveal that naltrexone has anticonvulsive properties and is a candidate drug for seizure treatment.
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