Description
Fenfluramine is the only marketed anorectic
agent that exerts its appetite depressant effect
via a serotoninrgic mechanism. Its
major metabolite, norfenfluramine, is believed
to be the main active form in humans .
Originator
Obenon,Neofarma
Definition
ChEBI: A secondary amino compound that is 1-phenyl-propan-2-amine in which one of the meta-hydrogens is substituted by trifluoromethyl, and one of the hydrogens attached to the nitrogen is substituted by an ethyl group. It binds to the serotonin reu
take pump, causing inhbition of serotonin uptake and release of serotonin. The resulting increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding
ehavior located in the hypothalamus. This suppresses the appetite for carbohydrates. Fenfluramine was used as the hydrochloride for treatment of diabetes and obesity. It was withdrawn worldwide after reports of heart valve disease and pulmonary hypertensio
.
Manufacturing Process
38.5 parts of (trifluoromethyl-3'-phenyl)-1-oximino-2-propane in 550 parts of
ethanol (with ammonia) was hydrogenated under pressure of hydrogen 90 kg
with a catalyst nickel Reney (20 parts). After a completion of reaction to the
reaction mixture was added 1000 parts of water and 300 parts of hydrochloric
acid. The mixture was concentrated in vacuo and extracted with 450 parts of
ether. To an aqueous phase was added the sodium carbonate and the mixture
was extracted with 500 parts of ether. Organic phase was concentrated in
vacuo to obtain 29 g of 1-(meta-trifluoromethyl-phenyl)-2-ethylaminopropane.
B.P. 96°C at 17 mm.
Brand name
Pondimin (Robins).
Therapeutic Function
Anorexic
World Health Organization (WHO)
Fenfluramine, dexfenfluramine and phentermine were approved
individually more than 20 years ago in the USA for single-drug, short-term
treatment of obesity. The manufacturers of fenfluramine and dexfenfluramine have
since voluntarily withdrawn both products from the market worldwide.
Phentermine remains available.
Synthesis
Fenfluramine is prepared by reductive alkylation
of norfenfluramine with acetaldehyde .
The nor compound is obtained by catalytic
hydrogenation of the oxime made from 3-trifluoromethlyphenyl
acetone (Eq. 2).
