Fenfluramine

Fenfluramine
Fenfluramine
Systematic (IUPAC) name
(RS)-N-ethyl- 1-[3-(trifluoromethyl)phenyl]propan- 2-amine
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat. C(US)
Legal status Schedule IV
Routes Oral
Pharmacokinetic data
Half-life 20 hours
Identifiers
CAS number 458-24-2 YesY
ATC code A08AA02
PubChem CID 3337
DrugBank 3337
ChemSpider 3220 YesY
UNII 2DS058H2CF YesY
KEGG D07945 YesY
ChEBI CHEBI:5000 YesY
ChEMBL CHEMBL87493 YesY
Chemical data
Formula C12H16F3N 
Mol. mass 231.26 g/mol
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

Fenfluramine (3-trifluoromethyl-N-ethylamphetamine, trade names Pondimin, Ponderax and Adifax) is a drug that was part of the Fen-Phen anti-obesity medication (the other drug being phentermine). Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine. It increases the level of the neurotransmitter serotonin, a chemical 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.[1] The end result is a feeling of fullness and loss of appetite.

Contents

Withdrawal due to heart disease

The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease,[2][3] and pulmonary hypertension, including a condition known as cardiac fibrosis. After the US withdrawal of fenfluramine, it was also withdrawn from other markets around the world.

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 agonist of 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-HT2B receptors.[4][5]

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.[6] 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.

See also

References

  1. ^ Nestler, Eric J. "Molecular Neuropharmacology: A Foundation for Clinical Neuroscience" McGraw-Hill, 2001.
  2. ^ Connolly HM, Crary JL, McGoon MD, et al (1997). "Valvular heart disease associated with fenfluramine-phentermine". N. Engl. J. Med. 337 (9): 581–8. doi:10.1056/NEJM199708283370901. PMID 9271479. http://content.nejm.org/cgi/content/full/337/9/581. 
  3. ^ Weissman NJ (2001). "Appetite suppressants and valvular heart disease". Am. J. Med. Sci. 321 (4): 285–91. doi:10.1097/00000441-200104000-00008. PMID 11307869. 
  4. ^ Roth BL (2007). "Drugs and valvular heart disease". N. Engl. J. Med. 356 (1): 6–9. doi:10.1056/NEJMp068265. PMID 17202450. 
  5. ^ Rothman, Richard B; Baumann, Michael H (2009). "Serotonergic drugs and valvular heart disease". Expert Opinion on Drug Safety 8 (3): 317–329. doi:10.1517/14740330902931524. PMC 2695569. PMID 19505264. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2695569.  edit
  6. ^ Dahl CF, Allen MR, Urie PM, Hopkins PN (2008). "Valvular regurgitation and surgery associated with fenfluramine use: an analysis of 5743 individuals". BMC Med 6: 34. doi:10.1186/1741-7015-6-34. PMC 2585088. PMID 18990200. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2585088. 

Further reading

  • Welch JT, Lim DS (November 2007). "The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine". Bioorg. Med. Chem. 15 (21): 6659–66. doi:10.1016/j.bmc.2007.08.012. PMID 17765553. 

External links

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Look at other dictionaries:

  • Fenfluramine — Énantiomère S de la fenfluramine (en haut) et (R) fenfluramine (en bas) Général …   Wikipédia en Français

  • fenfluramine — noun Etymology: fen (alteration of phen ) + flur (alteration of fluor ) + amine Date: 1965 an anorectic amphetamine derivative C12H16F3N with little stimulant effect on the central nervous system formerly used in the form of its hydrochloride to… …   New Collegiate Dictionary

  • fenfluramine — /fen floor euh meen /, n. Pharm. a sympathomimetic substance, C12H16F3N, used mainly as an anorectic in the treatment of obesity. [1965 70; by contr., resp. and rearrangement of (trifluoromethyl)phenethylamine] * * * …   Universalium

  • fenfluramine — noun A appetite suppressant used to treat obesity …   Wiktionary

  • fenfluramine — fen·flur·amine .fen flu̇r ə .mēn n an anorectic amphetamine derivative C12H16F3N with little stimulant effect on the central nervous system formerly used in the form of its hydrochloride to treat obesity but no longer used due to its association… …   Medical dictionary

  • fenfluramine — fen·flur·amine …   English syllables

  • fenfluramine — /fɛnˈflurəmin/ (say fen floohruhmeen) noun a drug, usually combined with phentermine, which stimulates the production of serotonin and diminishes appetite; use as a recommended weight loss medication discontinued because of adverse side effects… …  

  • fenfluramine — fenˈflu̇rəˌmēn, mə̇n noun Etymology: fen (alteration of phen ) + flur (alteration of fluor ) + amine : an anorectic amphetamine derivative C12H16F3N with little stimulant effect on the central nervous system formerly used in the form of its… …   Useful english dictionary

  • fenfluramine hydrochloride — An anorexigenic agent …   Medical dictionary

  • Фенфлюрамин (Fenfluramine) — лекарственное вещество, аналогичное амфетамину; снижает аппетит; применяется для лечения ожирения. Назначается внутрь; возможные побочные эффекты: сонливость, понос. Торговое название: пондеракс (Ponderax). Источник: Медицинский словарь …   Медицинские термины

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