Both fenfluramine and de-ethylated fenfluramine decrease the brain stores of 5-hydroxytryptamine (5-HT). As the fenfluramine metabolite is present in the brain of the rat after fenfluramine injection, it could be suggested that the depletion of brain 5-HT elicited by fenfluramine is mediated by its metabolite. Comparative studies on 5-HT lowering effects and drug brain levels, indicate a primary effect of fenfluramine, following by the rising involvement of the de-ethylated compound in the sustained effect.
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Curr Neuropharmacol
January 2025
Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.
Epilepsy is a neurological disorder affecting millions of people worldwide. Antiseizure medications (ASM) remain a critical therapeutic intervention for treating epilepsy, notwithstanding the rapid development of other therapies. There have been substantial advances in epilepsy medications over the past three decades, with over 20 ASMs now available commercially.
View Article and Find Full Text PDFPediatr Neurol
January 2025
Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Pediatrics Research Group, Institut de Recerca Sant Pau (IR-Sant Pau), Barcelona, Spain; Pediatric Neurology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Background: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy associated with loss-of-function variants in the SCN1A gene. Although predominantly expressed in the central nervous system, SCN1A is also expressed in the heart, suggesting a potential link between neuronal and cardiac channelopathies. Additionally, DS carries a high risk of sudden unexpected death in epilepsy (SUDEP).
View Article and Find Full Text PDFEpilepsy Behav
January 2025
Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address:
Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy marked by drug-resistant seizures and profound cognitive and behavioral impairments, with nearly 95% of individuals affected by moderate to severe intellectual disability. This review comprehensively explores the cognitive and behavioral impacts of current treatment options for LGS, including antiseizure medications (ASMs), neuromodulation strategies, the ketogenic diet, and surgical interventions. Given the limited availability of LGS-specific data for several ASMs, the evidence base is supplemented with findings from general epilepsy populations and individuals with epilepsy and intellectual disabilities.
View Article and Find Full Text PDFEpilepsy Behav
January 2025
Department of Neurosurgery, Mass General Brigham, Harvard Medical School, Boston, MA 02115, USA.
Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, specific electroencephalogram (EEG) patterns, and significant cognitive and behavioral impairments. To date, eight anti-seizure medications (ASMs) have been specifically approved by the U.S.
View Article and Find Full Text PDFEpilepsia
December 2024
Department of Neuroscience and Medical Genetics, Children's Hospital Meyer IRCCS, Florence, Italy.
Objective: Fenfluramine (FFA), stiripentol (STP), and cannabidiol (CBD) are approved add-on therapies for seizures in Dravet syndrome (DS). We report on the long-term safety and health care resource utilization (HCRU) of patients with DS treated with FFA under an expanded access program (EAP).
Methods: A cohort of 124 patients received FFA for a median of 2.
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