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6-Fluoro-DMT

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6-Fluoro-DMT
Clinical data
Other names6-Fluoro-N,N-dimethyltryptamine; 6-Fluoro-DMT; 6-F-DMT; 6F-DMT
Drug classSerotonin receptor modulator
ATC code
  • None
Identifiers
  • 2-(6-fluoro-1H-indol-3-yl)-N,N-dimethyl-ethanamine
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC12H15FN2
Molar mass206.264 g·mol−1
3D model (JSmol)
  • CN(CCC1=CNC2=C1C=CC(F)=C2)C
  • InChI=1S/C12H15FN2/c1-15(2)6-5-9-8-14-12-7-10(13)3-4-11(9)12/h3-4,7-8,14H,5-6H2,1-2H3 checkY
  • Key:DZXZPVGWRZCXDH-UHFFFAOYSA-N checkY
  (verify)

6-Fluoro-DMT, also known as 6-fluoro-N,N-dimethyltryptamine, is a synthetic serotonin receptor modulator of the tryptamine family.[1][2]

Effects

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6-Fluoro-DMT has been said to not be active as a hallucinogen in humans.[3] It has been claimed that this is due to it being "metabolically blocked", though this was not further elaborated on.[3] In the 1960s, it had been theorized by Stephen Szára and colleagues that psychedelic tryptamines were prodrugs that required 6-hydroxylation to become hallucinogenic, but this theory was later found to be incorrect.[4][5][6][7] 6-Fluoro-DMT has been thought to be inactive as a psychedelic in part because 6-fluoro-DET is inactive in terms of such effects.[8][9][10][11][12]

Pharmacology

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6-Fluoro-DMT activities
Target Affinity (Ki, nM)
5-HT1A 693–865 (Ki)
IA (EC50Tooltip half-maximal effective concentration)
5-HT1B 218
5-HT1D 55
5-HT1E 461
5-HT1F ND
5-HT2A 511–866 (Ki)
41–16,830 (EC50)
74% (EmaxTooltip maximal efficacy)
5-HT2B 30
5-HT2C 674 (Ki)
1.252–5.816 (EC50)
105–131% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A 961
5-HT6 26
5-HT7 41
α1A 173
α1B >10,000
α1D ND
α2A >10,000
α2B 260
α2C 149
β1 >10,000
β2 >10,000
β3 ND
D1 547
D2 610
D3 867
D4 1,454
D5 6,291
H1 47
H2 925
H3, H4 >10,000
M1–M5 >10,000
I1 898
σ1 6,892
σ2 7,128
TAAR1Tooltip Trace amine-associated receptor 1 ND
SERTTooltip Serotonin transporter 145 (Ki)
NETTooltip Norepinephrine transporter >10,000 (Ki)
DATTooltip Dopamine transporter >10,000 (Ki)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [13][2][14][15]

6-Fluoro-DMT is known to possess varying affinities for serotonin receptors, adrenergic receptors, dopamine receptors, histamine receptors, the imidazoline I1 receptor, sigma receptors, and the serotonin transporter (SERT).[2] It has been found to be a potent partial agonist of the serotonin 5-HT2A receptor and a potent full agonist of the serotonin 5-HT2C receptor.[2] In another study however, it showed affinity for the serotonin 5-HT1A and 5-HT2A receptors but was inactive as a serotonin 5-HT1A receptor agonist and showed low potency as a serotonin 5-HT2A receptor agonist.[14][15] On the other hand, it was only about 3-fold less potent than dimethyltryptamine (DMT) as a serotonin 5-HT2A receptor agonist in this study.[15] 6-Fluoro-DMT is less active than dimethyltryptamine (DMT) in producing effects in animal studies.[1][16]

History

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6-Fluoro was first described in the scientific literature by at least 1966.[1][16][3]

See also

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References

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  1. ^ a b c Shulgin AT (1976). "Psychotomimetic Agents". In Gordon M (ed.). Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. Vol. 4. Academic Press. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN 978-0-12-290559-9. This metabolically available site (6 position) was blocked with a fluoro-group in a number of these N,N-dialkyltryptamines. 6-Fluoro-N,N-dimethyltryptamine [(XXXVI), R = CH3] was again found to be less active than the parent N,N-dimethyltryptamine in animal studies (Kalir and Szara, 1966). However, clinical studies with the ethyl homolog [(XXXVI), R = C2H5] has shown that it produces most of the somatic effects of the comparison drug N,N-dipropyltryptamine without any of the psychological changes. It is proposed as an "active placebo" in controlling experiments with possible hallucinogenics (Faillace et al., 1967). The present evidence indicates that chemical substitution on the 6 position of the tryptamine system destroys the psychotomimetic potential of the compound.
  2. ^ a b c d Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2): e9019. Bibcode:2010PLoSO...5.9019R. doi:10.1371/journal.pone.0009019. PMC 2814854. PMID 20126400.
  3. ^ a b c Kline TB (1980). Structure-Activity Relationships Of N,N-Dialkyltryptamines Substituted In The Benzene Moiety (Ph.D. thesis). University of Alabama at Birmingham. Retrieved 15 November 2024 – via UAB Digital Commons. Neither 6-hydroxy DMT, 5-methoxy-6-hydroxy DMT, nor the metabolically blocked 6-fluoro DMT are active hallucinogens in man.
  4. ^ Szara S, Hearst E (1962). "The 6-Hydroxylation of Tryptamine Derivatives: A Way of Producing Psychoactive Metabolites". Annals of the New York Academy of Sciences. 96 (1): 134–141. doi:10.1111/j.1749-6632.1962.tb50108.x. ISSN 0077-8923. Retrieved 8 April 2025.
  5. ^ Szara S, Hearst E, Putney F (1962). "Metabolism and behavioural action of psychotropic tryptamine homologues". International Journal of Neuropharmacology. 1 (1–3): 111–117. doi:10.1016/0028-3908(62)90015-1. Retrieved 8 April 2025.
  6. ^ Szara S, Rockland LH, Rosenthal D, Handlon JH (September 1966). "Psychological effects and metabolism of N,N-diethyltryptamine in man". Arch Gen Psychiatry. 15 (3): 320–329. doi:10.1001/archpsyc.1966.01730150096014. PMID 5330062.
  7. ^ Taborsky RG, Delvigs P, Page IH (August 1966). "6-hydroxylation: effect on the psychotropic potency of tryptamines". Science. 153 (3739): 1018–1020. doi:10.1126/science.153.3739.1018. PMID 5917552.
  8. ^ Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, et al. (2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nature Communications. 14 (1): 8221. doi:10.1038/s41467-023-43904-4 (inactive 6 July 2025). PMC 10694965. PMID 38001451.{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)
  9. ^ "Psychedelic-Inspired Medium-Throughput Assays for the Development of Next-Generation Neurotherapeutics". ProQuest. 6-F-DMT has been thought to be non-hallucinogenic as 6-F-DET (6-fluoro-N,N-diethyltryptamine) has been shown to not substitute for LSD in DD.
  10. ^ "Fluorinated tryptamine compounds, analogues thereof, and methods using same". Google Patents. 2 June 2022. Retrieved 8 April 2025.
  11. ^ Shulgin A, Shulgin A (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252.
  12. ^ Faillace LA, Vourlekis A, Szara S (October 1967). "Clinical evaluation of some hallucinogenic tryptamine derivatives". J Nerv Ment Dis. 145 (4): 306–313. doi:10.1097/00005053-196710000-00005. PMID 6076017.
  13. ^ "Kᵢ Database". PDSP. 22 March 2025. Retrieved 22 March 2025.
  14. ^ a b Chen X, Li J, Yu L, Maule F, Chang L, Gallant JA, et al. (October 2023). "A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines". J Biol Chem. 299 (10) 105231. doi:10.1016/j.jbc.2023.105231. PMC 10570959. PMID 37690691.
  15. ^ a b c Chen X, Li J, Yu L, Dhananjaya D, Maule F, Cook S, et al. (10 March 2023), Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery (PDF), doi:10.21203/rs.3.rs-2667175/v1, retrieved 18 March 2025
  16. ^ a b Kalir A, Szara S (May 1966). "Synthesis and pharmacological activity of alkylated tryptamines" (PDF). J Med Chem. 9 (3): 341–344. doi:10.1021/jm00321a017. PMID 5960901.
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