Fenfluramine

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Fenfluramine
Systematic (IUPAC) name
N-ethyl-1-[3-(trifluoromethyl)- phenyl]propan-2-amine
Identifiers
CAS number	458-24-2
ATC code	A08AA02
PubChem	3337
DrugBank	APRD00319
Chemical data
Formula	C₁₂H₁₆F₃N
Mol. mass	231.257
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Half life	20 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	? (United States) ? (Australia)
Legal status	Unscheduled, Withdrawn from market
Routes	Oral

Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication (the other drug being phentermine). Also known as Pondimin, fenfluramine was introduced on the U.S. market in 1973. It is the racemic form of dexfenfluramine. It is designed to increase the level of the neurotransmitter serotonin. This depresses the central nervous system, regulating mood and appetite. The end result is a feeling of fullness and loss of 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The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease and pulmonary hypertension, including a condition known as cardiac fibrosis.

The distinctive valvular abnormality seen with fenfluramine is a thickening of the leaflet and chordae tendinae. Roth (2007) suggested a mechanism by which fenfluramine damaged the valves. Heart valves also have serotonin receptors, which regulate their growth. He reported that fenfluramine and its active metabolite norfenfluramine stimulated the serotonin receptors 5-hydroxytryptamine (5-HT). In particular norfenfluramine is a potent agonist (stimulant) of 5-HT_2B receptors. These receptors are plentiful in human cardiac valves and appear to be essential for normal cardiac development. Roth suggested that the mechanism by which fenfluramine causes damage is through inappropriately stimulating the valve cells to divide. This valve damage is found in other drugs that act on 5-HT_2B receptors.