Norfenfluramine

Norfenfluramine
Clinical data
Other names	3-Trifluoromethylamphetamine; 3-TFMA; Desethylfenfluramine; JP-92
Identifiers
	IUPAC name 1-[3-(trifluoromethyl)phenyl]propan-2-amine;
CAS Number	19036-73-8 ;
PubChem CID	15897;
IUPHAR/BPS	215;
ChemSpider	15108 ;
UNII	CLX07A6ZIY;
ChEBI	CHEBI:125411;
ChEMBL	ChEMBL1979333;
CompTox Dashboard (EPA)	DTXSID60904717 ;
Chemical and physical data
Formula	C10H12F3N
Molar mass	203.208 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES FC(F)(F)c1cccc(c1)CC(N)C;
	InChI InChI=1S/C10H12F3N/c1-7(14)5-8-3-2-4-9(6-8)10(11,12)13/h2-4,6-7H,5,14H2,1H3 ; Key:MLBHFBKZUPLWBD-UHFFFAOYSA-N ;
	(verify)

Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family that behaves as a serotonin and norepinephrine releasing agent and potent 5-HT_2A, 5-HT_2B, and 5-HT_2C agonist. The action of norfenfluramine on 5-HT_2B receptors on heart valves leads to a characteristic pattern of heart failure following proliferation of cardiac fibroblasts on the tricuspid valve, known as cardiac fibrosis.^[1] This side effect led to the withdrawal of fenfluramine as an anorectic agent worldwide, and to the withdrawal of benfluorex in Europe,^[2] as both fenfluramine and benfluorex form norfenfluramine as an active metabolite. It is a human TAAR1 agonist.^[3]

In spite of acting as a serotonin 5-HT_2A receptor agonist, norfenfluramine is described as non-hallucinogenic.^[4] However, hallucinations have occasionally been reported with large doses of fenfluramine, which itself is a much weaker serotonin 5-HT_2A receptor agonist than norfenfluramine but produces norfenfluramine as a major active metabolite.^[4]

References

^ Setola V, Dukat M, Glennon RA, Roth BL (July 2005). "Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptor". Molecular Pharmacology. 68 (1): 20–33. doi:10.1124/mol.104.009266. PMID 15831837. S2CID 30906680.
^ "European Medicines Agency recommends withdrawal of benfluorex from the market in European Union" (PDF). European Medicines Agency. 2009-12-18. Archived from the original (PDF) on 2009-12-22.
^ Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorganic & Medicinal Chemistry. 19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007. PMC 3236098. PMID 22037049.
^ ^a ^b Gumpper RH, Roth BL (January 2024). "Psychedelics: preclinical insights provide directions for future research". Neuropsychopharmacology. 49 (1): 119–127. doi:10.1038/s41386-023-01567-7. PMID 36932180.

[1] Setola V, Dukat M, Glennon RA, Roth BL (July 2005). "Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptor". Molecular Pharmacology. 68 (1): 20–33. doi:10.1124/mol.104.009266. PMID 15831837. S2CID 30906680.

[2] "European Medicines Agency recommends withdrawal of benfluorex from the market in European Union" (PDF). European Medicines Agency. 2009-12-18. Archived from the original (PDF) on 2009-12-22.

[pmid22037049-3] Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorganic & Medicinal Chemistry. 19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007. PMC 3236098. PMID 22037049.

[GumpperRoth2024-4] Gumpper RH, Roth BL (January 2024). "Psychedelics: preclinical insights provide directions for future research". Neuropsychopharmacology. 49 (1): 119–127. doi:10.1038/s41386-023-01567-7. PMID 36932180.

[1]

[2]

[3]

[4]

Norfenfluramine

See also

References