Fenfluramine acts as a positive modulator of sigma-1 receptors.

Adjunctive fenfluramine hydrochloride, classically described as acting pharmacologically through a serotonergic mechanism, has demonstrated a unique and robust clinical response profile with regard to its magnitude, consistency, and durability of effect on seizure activity in patients with pharmacoresistant Dravet syndrome. Recent findings also support long-term improvements in executive functions (behavior, emotion, cognition) in these patients. The observed clinical profile is inconsistent with serotonergic activity alone, as other serotonergic medications have not been demonstrated to have these clinical effects. This study investigated a potential role for σ Radioligand binding assays tested the affinity of fenfluramine for 47 receptors associated with seizures in the literature, including σ receptors. Cellular function assays tested fenfluramine and norfenfluramine (its major metabolite) activity at various receptors, including adrenergic, muscarinic, and serotonergic receptors. The σ Fenfluramine and norfenfluramine bound ≥30% to β Fenfluramine demonstrated modulatory activity at σ

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Déclaration de conflit d'intérêts

Declaration of competing interest Dr. Martin, Dr. Gammaitoni, Dr. Farfel, and Dr. Galer are employees of, and/or own stock in, Zogenix, Inc. Dr. de and Dr. Maurice Witte received consultancy fees from Zogenix. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.