Fenfluramine (former brand names Pondimin, Ponderax and Adifax), also known as 3-trifluoromethyl-N-ethylamphetamine, is an anorectic that is no longer marketed. In combination with phentermine, it was part of the anti-obesity medication Fen-phen. Fenfluramine was introduced on the U.S. market in 1973 and withdrawn in 1997. It is the racemic mixture of two enantiomers, dexfenfluramine, and levofenfluramine. The drug increases the level of serotonin, a neurotransmitter that regulates mood, appetite and other functions. Fenfluramine causes the release of serotonin by disrupting vesicular storage of the neurotransmitter and reversing serotonin transporter function. The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease and pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world. In this small exploratory and retrospective study, remarkably good results were reported on the use of fenfluramine as an add-on medication for controlling seizures in patients with the Dravet syndrome. The side effects were rare and nonserious and did not result in termination of the treatment. It is possible that this drug may have anticonvulsive effects for other severe epilepsy syndromes, especially in those characterized by photosensitive or induced seizures.

LEVOFENFLURAMINE is a levorotatory enantiomer of fenfluramine, a substituted amphetamine which was formerly used to treat obesity. LEVOFENFLURAMINE has dopamine-antagonistic properties and, at high doses, increases dopamine concentrations in rat striatal dialysates. It is essentially inactive to reduce food intake in human subjects.

Dexfenfluramine, also marketed under the name Redux, is a serotoninergic anorectic drug. Dexfenfluramine, the dextrorotatory isomer of fenfluramine, is indicated for use in the management of obesity in patients with a body mass index of > or = 30 kg/m2, or > or = 27 kg/m2 in the presence of other risk factors. Unlike fenfluramine, dexfenfluramine is a pure serotonin agonist. Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. Dexfenfluramine reduces blood pressure, percent glycosylated hemoglobin, and concentrations of blood glucose and blood lipids, but these benefits may be indirect. Dexfenfluramine may also be of some value in controlling eating habits in diabetic patients, preventing weight gain after smoking cessation, and treating bulimia, seasonal affective disorder, neuroleptic-induced obesity, and premenstrual syndrome. Dexfenfluramine's most frequent adverse effects are insomnia, diarrhea, and headache; it has also been associated with primary pulmonary hypertension. The drug should not be combined with other serotonergic agonists because of the risk of serotonin syndrome. The recommended dosage is 15 mg twice daily. Dexfenfluramine is effective in the treatment of obesity in selected patients. Because its efficacy is lost after six months of continuous treatment, it should be viewed primarily as an adjunct to diet and exercise. Dexfenfluramine was approved by the FDA in 1996 and has been widely used for the treatment of obesity. However, Dexfenfluramine was removed from the U.S. market in 1997 following reports of valvular heart disease and pulmonary hypertension.