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Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine

Epilepsy is among the most common neurological chronic disorders, with a prevalence of 0.5–1%. Despite the introduction of new antiepileptic drugs during recent years, about one third of the epileptic population remain drug-resistant. Hence, especially in the pediatric population limited by differen...

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Autores principales: Dini, Gianluca, Tulli, Eleonora, Dell’Isola, Giovanni Battista, Mencaroni, Elisabetta, Di Cara, Giuseppe, Striano, Pasquale, Verrotti, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164301/
https://www.ncbi.nlm.nih.gov/pubmed/35668937
http://dx.doi.org/10.3389/fphar.2022.832929
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author Dini, Gianluca
Tulli, Eleonora
Dell’Isola, Giovanni Battista
Mencaroni, Elisabetta
Di Cara, Giuseppe
Striano, Pasquale
Verrotti, Alberto
author_facet Dini, Gianluca
Tulli, Eleonora
Dell’Isola, Giovanni Battista
Mencaroni, Elisabetta
Di Cara, Giuseppe
Striano, Pasquale
Verrotti, Alberto
author_sort Dini, Gianluca
collection PubMed
description Epilepsy is among the most common neurological chronic disorders, with a prevalence of 0.5–1%. Despite the introduction of new antiepileptic drugs during recent years, about one third of the epileptic population remain drug-resistant. Hence, especially in the pediatric population limited by different pharmacokinetics and pharmacodynamics and by ethical and regulatory issues it is needed to identify new therapeutic resources. New molecules initially used with other therapeutic indications, such as fenfluramine, are being considered for the treatment of pharmacoresistant epilepsies, including Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). Drug-refractory seizures are a hallmark of both these conditions and their treatment remains a major challenge. Fenfluramine is an amphetamine derivative that was previously approved as a weight loss drug and later withdrawn when major cardiac adverse events were reported. However, a new role of fenfluramine has emerged in recent years. Indeed, fenfluramine has proved to be a promising antiepileptic drug with a favorable risk–benefit profile for the treatment of DS, LGS and possibly other drug-resistant epileptic syndromes. The mechanism by which fenfluramine provide an antiepileptic action is not fully understood but it seems to go beyond its pro-serotoninergic activity. This review aims to provide a comprehensive analysis of the literature, including ongoing trials, regarding the efficacy and safety of fenfluramine as adjunctive treatment of pharmacoresistant epilepsies.
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spelling pubmed-91643012022-06-05 Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine Dini, Gianluca Tulli, Eleonora Dell’Isola, Giovanni Battista Mencaroni, Elisabetta Di Cara, Giuseppe Striano, Pasquale Verrotti, Alberto Front Pharmacol Pharmacology Epilepsy is among the most common neurological chronic disorders, with a prevalence of 0.5–1%. Despite the introduction of new antiepileptic drugs during recent years, about one third of the epileptic population remain drug-resistant. Hence, especially in the pediatric population limited by different pharmacokinetics and pharmacodynamics and by ethical and regulatory issues it is needed to identify new therapeutic resources. New molecules initially used with other therapeutic indications, such as fenfluramine, are being considered for the treatment of pharmacoresistant epilepsies, including Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). Drug-refractory seizures are a hallmark of both these conditions and their treatment remains a major challenge. Fenfluramine is an amphetamine derivative that was previously approved as a weight loss drug and later withdrawn when major cardiac adverse events were reported. However, a new role of fenfluramine has emerged in recent years. Indeed, fenfluramine has proved to be a promising antiepileptic drug with a favorable risk–benefit profile for the treatment of DS, LGS and possibly other drug-resistant epileptic syndromes. The mechanism by which fenfluramine provide an antiepileptic action is not fully understood but it seems to go beyond its pro-serotoninergic activity. This review aims to provide a comprehensive analysis of the literature, including ongoing trials, regarding the efficacy and safety of fenfluramine as adjunctive treatment of pharmacoresistant epilepsies. Frontiers Media S.A. 2022-05-20 /pmc/articles/PMC9164301/ /pubmed/35668937 http://dx.doi.org/10.3389/fphar.2022.832929 Text en Copyright © 2022 Dini, Tulli, Dell’Isola, Mencaroni, Di Cara, Striano and Verrotti. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Dini, Gianluca
Tulli, Eleonora
Dell’Isola, Giovanni Battista
Mencaroni, Elisabetta
Di Cara, Giuseppe
Striano, Pasquale
Verrotti, Alberto
Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine
title Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine
title_full Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine
title_fullStr Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine
title_full_unstemmed Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine
title_short Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine
title_sort improving therapy of pharmacoresistant epilepsies: the role of fenfluramine
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164301/
https://www.ncbi.nlm.nih.gov/pubmed/35668937
http://dx.doi.org/10.3389/fphar.2022.832929
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