出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/25 00:11:56」(JST)[Wiki en表示]
|Systematic (IUPAC) name|
|(RS)-N-ethyl- 1-[3-(trifluoromethyl)phenyl]propan- 2-amine|
|Pregnancy cat.||B2 (AU) C (US)|
|Legal status||Prescription Only (S4) (AU) Schedule IV (US)|
|Mol. mass||231.26 g/mol|
| Y (what is this?)
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. The result is a feeling of fullness and loss of 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The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease, and pulmonary hypertension, including a condition known as cardiac fibrosis. After the US withdrawal of fenfluramine, it was also withdrawn from other markets around the world.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.
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.
See also 
- Nestler, E. J. (2001). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience. McGraw-Hill.
- 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.
- 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.
- Roth, B. L. (2007). "Drugs and Valvular Heart Disease". New England Journal of Medicine 356 (1): 6–9. doi:10.1056/NEJMp068265. PMID 17202450.
- 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.
- 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 
- 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.
- RxList.com - Fenfluramine
- Inchem.org - Fenfluramine
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- Halford JC, Boyland EJ, Lawton CL, Blundell JE, Harrold JA.SourceExperimental Psychology, University of Liverpool, Liverpool, UK.
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- The role of serotonin (5-hydroxytryptamine) in appetite control is long established. Serotonergic manipulations reduce food intake in rodents in a manner consistent with satiety. In humans, drugs such as fenfluramine, dexfenfluramine and sibutramine all reduce energy intake, suppress hunger and enha
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- Effects of fenfluramine, 8-OH-DPAT, and tryptophan-enriched diet on the high-ethanol intake by rats bred for susceptibility to stress.
- West CH, Boss-Williams KA, Weiss JM.SourceDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30306, USA.
- Alcohol (Fayetteville, N.Y.).Alcohol.2011 Dec;45(8):739-49. Epub 2011 Sep 15.
- The swim-test susceptible (SUS) line of rats has been bred in our laboratory for the characteristic of reduced motor activity in the swim test following exposure to an acute stressor. Testing of multiple generations of SUS rats has also revealed that they consume large amounts of ethanol voluntarily
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- YAKUGAKU ZASSHI 134(2), 197-202, 2014
- NAID 130003391159
- Enhanced Behavioral Response to Serotonin-Related Agonists in Postweaning Protein Malnourished Mice
- Biological and Pharmaceutical Bulletin 35(10), 1697-1702, 2012
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- In vivo incorporation of fenfluramine and norfenfluramine into pigmented and nonpigmented hair of rats measured by HPLC-fluorescence detection
- Forensic Toxicology 29(1), 44-50, 2011-01
- NAID 120003751805
- 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. ...
- During the 1990s, the commonly used weight-loss drug combination of fenfluramine and phenteramine was, is some patients, associated with the development of thickedned plaques on the cardiac valves. These patients were prone to develop MR, as well as aortic regurgitaion and tricuspid valve disease. (PPC. 204)