ArticleEpilepsia2025
Enantioselective comparative analysis of the anticonvulsant potency of fenfluramine and norfenfluramine in mice.
Article in Epilepsia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe in vivo effects of fenfluramine result from the combined actions of four active molecular entities (l-fenfluramine, d-fenfluramine, and the corresponding enantiomers of the primary metabolite norfenfluramine). Each of these compounds has different properties, with cardiovascular toxicity risk being ascribed primarily to the d-enantiomers. To determine whether l-fenfluramine or l-norfenfluramine is a better candidate for development as an enantiomerically pure antiseizure medication, we investigated dose-response and brain/plasma concentration-response relationships for each of the four individual enantiomers in mice.
methodsAntiseizure activity was evaluated in the maximal electroshock (MES) model at the time of peak effect. Neurotoxicity was assessed by determining minimal motor impairment (MMI) in the rotarod test. Median effective dose (ED
resultsThe four enantiomers differed in antiseizure potency and neurotoxic activity. d-Norfenfluramine had the highest potency, but it also had the highest toxicity and the lowest PI. Differences in antiseizure potency and toxicity estimated from plasma and brain concentrations were more prominent than those estimated based on dose. l-Fenfluramine had greater potency than d-fenfluramine and l-norfenfluramine, and was overall the compound with the highest PI (6.3 based on dose, 41.6 based on plasma concentrations, and 39.2 based on brain concentrations). SIGNIFICANCE: These findings are relevant in determining which enantiomer is most suitable for clinical development as a stereoselectively pure follow-up compound to the marketed racemic fenfluramine, and indicate that l-fenfluramine has superior antiseizure activity over l-norfenfluramine in the MES model. This study also illustrates the limitations of relying solely on dose-response curves, and the added value of assessing concentration-response relationships.
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