Fenfluramine

Fenfluramine

1 : 1 mixture (racemate)
Systematic (IUPAC) name
(RS)-N-ethyl- 1-[3-(trifluoromethyl)phenyl]propan- 2-amine
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: B2 US: C (Risk not ruled out)
Legal status	AU: S4 (Prescription only) US: Schedule IV
Routes of administration	Oral
Pharmacokinetic data
Biological half-life	20 hours
Identifiers
CAS Number	458-24-2 Y
ATC code	A08AA02 (WHO)
PubChem	CID: 3337
IUPHAR/BPS	4613
DrugBank	DB00574 Y
ChemSpider	3220 Y
UNII	2DS058H2CF Y
KEGG	D07945 Y
ChEBI	CHEBI:5000 Y
ChEMBL	CHEMBL87493 Y
Chemical data
Formula	C12H16F3N
Molecular mass	231.26 g/mol
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
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Fenfluramine (3-trifluoromethyl-N-ethylamphetamine, trade names Pondimin, Ponderax and Adifax) is a drug that, along with phentermine, 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Fenfluramine was introduced on the U.S. market in 1973 and withdrawn in 1997.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. It 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.

Withdrawal due to heart disease

The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease and pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world.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-HT2B 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.

According to a study of 5743 former users conducted by a plaintiff's expert cardiologist, damage to the heart valve continued long after stopping the medication. Of the users tested, 20 percent of women, and 12 percent of men were affected. For all ex-users, there was a sevenfold increase of chances of needing surgery for faulty heart valves caused by the drug.

Synthesis

Prepn: L. G. Beregi et al., FR M1658; eidem, US 3198833 (1963, 1965 both to Sci. Union et Cie Soc. Franc. Recherche Méd.). Prepn of optical isomers: eidem, US 3198834 (1965 to Sci. Union et Cie Soc. Franc. Recherche Med.).

See also

• Benfluorex

External links

• RxList.com - Fenfluramine
• Inchem.org - Fenfluramine
• circ.ahajournals.org