Fenfluramine

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Fenfluramine
Fenfluramine.svg
Systematic (IUPAC) name
(RS)-N-ethyl- 1-[3-(trifluoromethyl)phenyl]propan- 2-amine
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat. B2 (AU) C (US)
Legal status Prescription Only (S4) (AU) Schedule IV (US)
Routes Oral
Pharmacokinetic data
Half-life 20 hours
Identifiers
CAS number 458-24-2 YesY
ATC code A08AA02
PubChem CID 3337
DrugBank DB00574
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
 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 result is a feeling of fullness and loss of appetite.

Withdrawal due to heart disease[edit]

The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease,[2][3] and pulmonary hypertension, including a condition known as cardiac fibrosis. After the US withdrawal of fenfluramine, it was also withdrawn from other markets around the world. It was banned in India in 1998.[4]

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.[5][6]

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.[7] 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[edit]

References[edit]

  1. ^ Nestler, E. J. (2001). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience. McGraw-Hill. 
  2. ^ Connolly, H. M.; Crary, J. L.; McGoon, M. D.; Hensrud, D. D.; Edwards, B. S.; Edwards, W. D.; Schaff, H. V. (1997). "Valvular Heart Disease Associated with Fenfluramine-Phentermine". New England Journal of Medicine 337 (9): 581–588. doi:10.1056/NEJM199708283370901. PMID 9271479. 
  3. ^ Weissman, N. J. (2001). "Appetite Suppressants and Valvular Heart Disease". The American Journal of the Medical Sciences 321 (4): 285–291. doi:10.1097/00000441-200104000-00008. PMID 11307869. 
  4. ^ "Drugs banned in India". Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India. Retrieved 2013-09-17. 
  5. ^ Roth, B. L. (2007). "Drugs and Valvular Heart Disease". New England Journal of Medicine 356 (1): 6–9. doi:10.1056/NEJMp068265. PMID 17202450. 
  6. ^ Rothman, R. B.; Baumann, M. 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.  edit
  7. ^ Dahl, C. F.; Allen, M. R.; Urie, P. M.; Hopkins, P. N. (2008). "Valvular Regurgitation and Surgery Associated with Fenfluramine Use: An Analysis of 5743 Individuals" (pdf). BMC Medicine 6: 34. doi:10.1186/1741-7015-6-34. PMC 2585088. PMID 18990200. 

Further reading[edit]

  • Welch, J. T.; Lim, D. S. (2007). "The Synthesis and Biological Activity of Pentafluorosulfanyl Analogs of Fluoxetine, Fenfluramine, and Norfenfluramine". Bioorganic & Medicinal Chemistry 15 (21): 6659–6666. doi:10.1016/j.bmc.2007.08.012. PMID 17765553. 

External links[edit]