Norfenfluramine

Overview

Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family and a major active metabolite of the appetite suppressants fenfluramine and benfluorex. The compound is a racemic mixture of two enantiomers with differing activities, dexnorfenfluramine and levonorfenfluramine.[1][2] WP

Pharmacology

Pharmacology

Norfenfluramine acts as a serotonin–norepinephrine releasing agent (SNRA) and as a potent serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist. Both enantiomers of norfenfluramine are active as monoamine releasing agents, although dexnorfenfluramine is more potent than levonorfenfluramine. Similarly, both enantiomers are active as serotonin 5-HT₂ receptor agonists, but dexnorfenfluramine is likewise more potent than levonorfenfluramine.[1][3][4] WP

Norfenfluramine is of similar potency as fenfluramine as a serotonin releaser but is substantially more potent as a norepinephrine and dopamine releaser. The drug is also far more potent than fenfluramine as an agonist of the serotonin 5-HT₂ receptors.[1][3][4] WP

The action of norfenfluramine on serotonin 5-HT2B 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. This side effect led to the withdrawal of fenfluramine as an anorectic medication worldwide and to the withdrawal of benfluorex in Europe.[5][6] WP

In spite of acting as a serotonin 5-HT2A receptor agonist, norfenfluramine is described as non-hallucinogenic. However, hallucinations have occasionally been reported with large doses of fenfluramine, which itself is a much weaker serotonin 5-HT2A receptor agonist than norfenfluramine but produces norfenfluramine as a major active metabolite. Dexnorfenfluramine produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.[7][8] WP

Norfenfluramine has been found to act as an agonist of the trace amine-associated receptor 1 (TAAR1). Dexnorfenfluramine is a very weak human TAAR1 agonist (43% of maximum in screen at a concentration of 10,000 nM), whereas levonorfenfluramine is inactive as a human TAAR1 agonist.[9] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Chemistry

Formula

C10H12F3N PC

CAS number

1886-26-6 PC

Molar mass (g/mol)

203.20 PC

IUPAC name (computed by PubChem)

1-[3-(trifluoromethyl)phenyl]propan-2-amine PC

SMILES

CC(CC1=CC(=CC=C1)C(F)(F)F)N PC

InChIKey

MLBHFBKZUPLWBD-UHFFFAOYSA-N PC

PubChem CID

15897

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Rothman RB, Clark RD, Partilla JS, Baumann MH. (+)-Fenfluramine and its major metabolite, (+)-norfenfluramine, are potent substrates for norepinephrine transporters. The Journal of Pharmacology and Experimental Therapeutics. June 2003. doi:10.1124/jpet.103.049684 · PMID 12649307
2. Journal / agency Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL. 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro. Molecular Pharmacology. June 2003. doi:10.1124/mol.63.6.1223 · PMID 12761331
3. Journal / agency Rothman RB, Baumann MH. Therapeutic potential of monoamine transporter substrates. Current Topics in Medicinal Chemistry. 2006. doi:10.2174/156802606778249766 · PMID 17017961
4. Journal / agency Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL. Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. December 2000. doi:10.1161/01.cir.102.23.2836 · PMID 11104741
5. Journal / agency Setola V, Dukat M, Glennon RA, Roth BL. Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptor. Molecular Pharmacology. July 2005. doi:10.1124/mol.104.009266 · PMID 15831837
6. Other European Medicines Agency recommends withdrawal of benfluorex from the market in European Union. 2009-12-18
7. Journal / agency Gumpper RH, Roth BL. Psychedelics: preclinical insights provide directions for future research. Neuropsychopharmacology. January 2024. doi:10.1038/s41386-023-01567-7 · PMID 36932180 · PMC10700551
8. Journal / agency Vickers SP, Easton N, Malcolm CS, Allen NH, Porter RH, Bickerdike MJ, Kennett GA. Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5-HT(2C) receptor agonists. Pharmacol Biochem Behav. 2001. doi:10.1016/s0091-3057(01)00552-4 · PMID 11509227
9. Journal / agency Lewin AH, Miller GM, Gilmour B. Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class. Bioorganic & Medicinal Chemistry. December 2011. doi:10.1016/j.bmc.2011.10.007 · PMID 22037049 · PMC3236098

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.