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Clinical data
AHFS/Drugs.com International Drug Names
  • AU: B2
  • US: C (Risk not ruled out)
Routes of
ATC code
Legal status
Legal status
Pharmacokinetic data
Biological half-life 20 hours
CAS Number
PubChem CID
ECHA InfoCard 100.006.616
Chemical and physical data
Formula C12H16F3N
Molar mass 231.26 g/mol
3D model (Jmol)
Chirality Racemic mixture

Fenfluramine (former brand names Pondimin, Ponderax and Adifax), also known as 3-trifluoromethyl-N-ethylamphetamine, is an anorectic that is no longer marketed. In combination with phentermine, it was part of the anti-obesity medication Fen-phen.

Fenfluramine was introduced on the U.S. market in 1973 and withdrawn in 1997. It is the racemic mixture of two enantiomers, dexfenfluramine and levofenfluramine. The drug increases the level of serotonin, a neurotransmitter 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 reduced 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The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease[2][3] and pulmonary hypertension, including a condition known as cardiac fibrosis.[4] It was subsequently withdrawn from other markets around the world. It was banned in India in 1998.[5]

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 inhibitor of the re-uptake of 5-HT into nerve terminals.[6] 5-HT2B receptors. Fenfluramine and its active metabolite norfenfluramine affect the 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.[7][8]

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.[9] 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.

Other adverse effects and recreational use potential[edit]

There have been reports associating fenfluramine with depression, psychosis, exacerbation of pre-existing psychosis (schizophrenia), and sleep disturbances.[10] These effects may be mediated by serotonergic neurotoxicity/depletion of serotonin with chronic administration and/or activation 5-HT2A receptors.[10][11][12][13] In overdose, fenfluramine can result in serotonin syndrome and death.[14] Unlike various other amphetamine derivatives, fenfluramine is reported to be dysphoric, "unpleasantly lethargic", and non-addictive.[15] However, it has been reported to be used recreationally at high doses ranging between 80 and 400 mg, which have been described as producing euphoria, amphetamine-like effects, sedation, and hallucinogenic effects, along with anxiety, nausea, diarrhea, and sometimes panic attacks, as well as depressive symptoms once the drug had worn off.[15][16][17] At high doses (e.g., 240 mg, or between 200–600 mg), fenfluramine induces a psychedelic state resembling that produced by lysergic acid diethylamide (LSD).[17][18] While fenfluramine binds only very weakly to the 5-HT2 receptors, its active metabolite norfenfluramine binds to and activates the 5-HT2B and 5-HT2C receptors with high affinity and the 5-HT2A receptor with moderate affinity;[19][20] as such, indirect (via induction of serotonin release) and/or direct activation of the 5-HT2A receptor would be expected to be responsible for the psychedelic effects of the drug at sufficient doses.


Prepn: L. G. Beregi et al., FR M1658; eidem, US 3198833 (1963, 1965 both to Sci. Union et Cie Soc. Franc. Recherche Méd.). Prepn of optical isomers: eidem, US 3198834 (1965 to Sci. Union et Cie Soc. Franc. Recherche Med.).

See also[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. PMID 9271479. doi:10.1056/NEJM199708283370901. 
  3. ^ Weissman, N. J. (2001). "Appetite Suppressants and Valvular Heart Disease". The American Journal of the Medical Sciences. 321 (4): 285–291. PMID 11307869. doi:10.1097/00000441-200104000-00008. 
  4. ^ FDA September 15, 1997. FDA Announces Withdrawal Fenfluramine and Dexfenfluramine (Fen-Phen)
  5. ^ "Drugs banned in India". Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India. Archived from the original on 2015-02-21. Retrieved 2013-09-17. 
  6. ^ Vickers SP, Dourish CT, Kennett GA (2001). "Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors". Neuropharmacology. 41: 200–9. PMID 11489456. doi:10.1016/s0028-3908(01)00063-6. 
  7. ^ Roth, B. L. (2007). "Drugs and Valvular Heart Disease". New England Journal of Medicine. 356 (1): 6–9. PMID 17202450. doi:10.1056/NEJMp068265. 
  8. ^ Rothman, R. B.; Baumann, M. H. (2009). "Serotonergic Drugs and Valvular Heart Disease". Expert Opinion on Drug Safety. 8 (3): 317–329. PMC 2695569Freely accessible. PMID 19505264. doi:10.1517/14740330902931524. 
  9. ^ 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. PMC 2585088Freely accessible. PMID 18990200. doi:10.1186/1741-7015-6-34. 
  10. ^ a b James O'Donnell (Pharm. D.); Gopi Doctor Ahuja (2005). Drug Injury: Liability, Analysis, and Prevention. Lawyers & Judges Publishing Company. pp. 276–. ISBN 978-0-913875-27-8. 
  11. ^ Integrating the Neurobiology of Schizophrenia. Academic Press. 27 February 2007. pp. 142–. ISBN 978-0-08-047508-0. 
  12. ^ The Pharmacology of Corticotropin-releasing Factor (CRF). Effects on Sensorimotor Gating in the Rat. ProQuest. 2006. pp. 12–. ISBN 978-0-549-53661-1. 
  13. ^ Christian P. Muller; Barry Jacobs (30 December 2009). Handbook of the Behavioral Neurobiology of Serotonin. Academic Press. pp. 630–. ISBN 978-0-08-087817-1. 
  14. ^ Mann SC, Caroff SN, Keck PE, Lazarus A (20 May 2008). Neuroleptic Malignant Syndrome and Related Conditions. American Psychiatric Pub. pp. 111–. ISBN 978-1-58562-744-8. 
  15. ^ a b John Calvin M. Brust (2004). Neurological Aspects of Substance Abuse. Butterworth-Heinemann. pp. 117–. ISBN 978-0-7506-7313-6. 
  16. ^ United States. Congress. Senate. Select Committee on Small Business. Subcommittee on Monopoly and Anticompetitive Activities (1976). Competitive problems in the drug industry: hearings before Subcommittee on Monopoly and Anticompetitive Activities of the Select Committee on Small Business, United States Senate, Ninetieth Congress, first session. U.S. Government Printing Office. pp. 2–. 
  17. ^ a b Drug Addiction II: Amphetamine, Psychotogen, and Marihuana Dependence. Springer Science & Business Media. 27 November 2013. pp. 258–. ISBN 978-3-642-66709-1. 
  18. ^ Drug Addiction II: Amphetamine, Psychotogen, and Marihuana Dependence. Springer Science & Business Media. 27 November 2013. pp. 249–. ISBN 978-3-642-66709-1. 
  19. ^ Giuseppe Di Giovanni; Vincenzo Di Matteo; Ennio Esposito (2008). Serotonin-dopamine Interaction: Experimental Evidence and Therapeutic Relevance. Elsevier. pp. 393–. ISBN 978-0-444-53235-0. 
  20. ^ Fitzgerald LW, Burn TC, Brown BS, Patterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abbaszade I, Hollis JM, Largent BL, Hartig PR, Hollis GF, Meunier PC, Robichaud AJ, Robertson DW (2000). "Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine". Mol. Pharmacol. 57 (1): 75–81. PMID 10617681. 

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. PMID 17765553. doi:10.1016/j.bmc.2007.08.012. 

External links[edit]