Fenfluramine

Fenfluramine

Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: B2 US: C (Risk not ruled out)
Routes of administration	Oral
ATC code	A08AA02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: Schedule IV
Pharmacokinetic data
Biological half-life	20 hours
Identifiers
IUPAC name (RS)-N-ethyl- 1-[3-(trifluoromethyl)phenyl]propan- 2-amine
CAS Number	458-24-2 Y
PubChem CID	3337
IUPHAR/BPS	4613
DrugBank	DB00574 Y
ChemSpider	3220 Y
UNII	2DS058H2CF
KEGG	D07945 Y
ChEBI	CHEBI:5000 Y
ChEMBL	CHEMBL87493 Y
ECHA InfoCard	100.006.616
Chemical and physical data
Formula	C12H16F3N
Molar mass	231.26 g/mol
3D model (Jmol)	Interactive image
Chirality	Racemic mixture
SMILES FC(F)(C1=CC(CC(C)NCC)=CC=C1)F
InChI InChI=1S/C12H16F3N/c1-3-16-9(2)7-10-5-4-6-11(8-10)12(13,14)15/h4-6,8-9,16H,3,7H2,1-2H3 Y Key:DBGIVFWFUFKIQN-UHFFFAOYSA-N Y

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Fenfluramine was introduced on the U.S. market in 1973 and withdrawn in 1997.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 result is a feeling of fullness and reduced appetite.

The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease and pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world. It was banned in India in 1998.

The distinctive valvular abnormality seen with fenfluramine is a thickening of the leaflet and chordae tendineae. One mechanism used to explain this phenomenon involves heart valve serotonin receptors, which are thought to help regulate growth. Since fenfluramine and its active metabolite norfenfluramine stimulate serotonin receptors, this may have led to the valvular abnormalities found in patients using fenfluramine. In particular norfenfluramine is a potent inhibitor of the re-uptake of 5-HT into nerve terminals.5-HT_2B receptors. Fenfluramine and its active metabolite norfenfluramine affect the 5-HT_2B receptors which are plentiful in human cardiac valves. The suggested mechanism by which fenfluramine causes damage is through over or inappropriate stimulation of these receptors leading to inappropriate valve cell division. Supporting this idea is the fact that this valve abnormality has also occurred in patients using other drugs that act on 5-HT_2B receptors.