Pharmacokinetics
The elimination half-life of fenfluramine has been reported as ranging from 13 to 30 hours. The mean elimination half-lives of its enantiomers have been found to be 19 hours for dexfenfluramine and 25 hours for levfenfluramine. Norfenfluramine, the major active metabolite of fenfluramine, has an elimination half-life that is about 1.5 to 2 times as long as that of fenfluramine, with mean values of 34 hours for dexnorfenfluramine and 50 hours for levnorfenfluramine. Chemistry
Fenfluramine is a substituted amphetamine and is also known as 3-trifluoromethyl-N-ethylamphetamine. It is a racemic mixture of two enantiomers, dexfenfluramine and levofenfluramine. Some analogues of fenfluramine include norfenfluramine, benfluorex, flucetorex, and fludorex. History
Fenfluramine was developed in the early 1960s and was introduced in France in 1963. Approximately 50 million Europeans were treated with fenfluramine for appetite suppression between 1963 and 1996. Fenfluramine was approved in the United States in 1973. The combination of fenfluramine and phentermine was proposed in 1984. Approximately 5 million people in the United States were given fenfluramine or dexfenfluramine with or without phentermine between 1996 and 1998.In the early 1990s, French researchers reported an association of fenfluramine with primary pulmonary hypertension and dyspnea in a small sample of patients. Fenfluramine was withdrawn from the U.S. market in 1997 after reports of heart valve disease and continued findings of pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world. It was banned in India in 1998.Fenfluramine was an appetite suppressant which was used to treat obesity.
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 under the brand name Fen-Phen among others.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 releasing agent, agonist of the serotonin 5-HT2 receptors, and 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 σ1 receptor.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 is a schedule IV controlled substance in the United States.