Fenfluramine

Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treatment of obesity, but was discontinued for this use due to cardiovascular toxicity before being repurposed for new indications. Fenfluramine was used for weight loss both alone under the brand name Pondimin and in combination with phentermine commonly known as fen-phen. Side effects of fenfluramine in people treated for seizures include decreased appetite, somnolence, sedation, lethargy, diarrhea, constipation, abnormal echocardiogram, fatigue, malaise, asthenia, ataxia, balance disorder, gait disturbance, increased blood pressure, drooling, excessive salivation, fever, upper respiratory tract infection, vomiting, appetite loss, weight loss, falls, and status epilepticus. Fenfluramine acts as a serotonin and norepinephrine releasing agent, agonist of the serotonin 5-HT2 receptors, and sigma σ1 receptor positive modulator. Its mechanism of action in the treatment of seizures is unknown, but may involve increased activation of certain serotonin receptors and the sigma σ1 receptor. Chemically, fenfluramine is a phenethylamine and amphetamine. Fenfluramine was developed in the early 1960s and was first introduced for medical use as an appetite suppressant in France in 1963 followed by approval in the United States in 1973. In the 1990s, fenfluramine came to be associated with cardiovascular toxicity, and because of this, was withdrawn from the United States market in 1997. Subsequently, it was repurposed for the treatment of seizures and was reintroduced in the United States and the European Union in 2020. Fenfluramine was previously a schedule IV controlled substance in the United States. However, the substance has since no-longer been subject to control pursuant to rule-making issued on 23 December 2022.