6-Fluoro-DET

Last updated
6-Fluoro-DET
6-Fluoro-DET.svg
Clinical data
Other names
  • 6-F-DET
  • 6-Fluoro-N,N-diethyltryptamine
  • 1H-Indole-3-ethanamine, N,N-diethyl-6-fluoro-
Identifiers
  • N,N-diethyl-2-(6-fluoro-1H-indol-3-yl)ethanamine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C14H19FN2
Molar mass 234.318 g·mol−1
3D model (JSmol)
  • CCN(CC)CCC1=CNC2=C1C=CC(=C2)F
  • InChI=1S/C14H19FN2/c1-3-17(4-2)8-7-11-10-16-14-9-12(15)5-6-13(11)14/h5-6,9-10,16H,3-4,7-8H2,1-2H3
  • Key:RPWUTEXLVPDNEA-UHFFFAOYSA-N

6-Fluoro-DET (6F-DET, 6-fluoro-N,N-diethyltryptamine) is a substituted tryptamine derivative related to drugs such as DET and 5-fluoro-DET. It acts as a partial agonist at the 5-HT2A receptor, [1] but while it produces similar physiological effects to psychedelic drugs, it does not appear to produce psychedelic effects itself even at high doses. Relatedly, 6-F-DET does not substituted for LSD in drug discrimination tests and does not produce the head-twitch response in rodents. [1] [2] [3] For the preceding reasons, it saw some use as an active placebo in early clinical trials of psychedelic drugs but was regarded as having little use otherwise, [4] though more recent research into compounds such as AL-34662, TBG and zalsupindole has shown that these kind of non-psychedelic 5-HT2A agonists can have various useful applications. [5] [6] [7] [8] [9] [10]

A hypothesis for the lack of head-twitch response in mice and hallucinogenic effects in humans is that 6-F-DET acts as a 5-HT2A receptor partial agonist of the Gq signaling pathway. [1] This hypothesis explains the lack of hallucinogenic effects of other 5-HT2A receptor ligands, which are also weak Gq agonists and below the efficacy threshold found to induce psychedelic effects, like 25N-N1-Nap, 2-Br-LSD, lisuride, tabernanthalog, and 6-MeO-DMT. [1] [9] [11]


See also

References

  1. 1 2 3 4 Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar RJ, Halberstadt AL, McCorvy JD (2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nature Communications. 14 (1): 8221. doi:10.1038/s41467-023-43904-4. PMC   10694965 . PMID   38001451.
  2. ↑ "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.
  3. ↑ "Fluorinated tryptamine compounds, analogues thereof, and methods using same". Google Patents. 2 June 2022. Retrieved 8 April 2025.
  4. ↑ Faillace LA, Vourlekis A, Szara S (October 1967). "Clinical evaluation of some hallucinogenic tryptamine derivatives". The Journal of Nervous and Mental Disease. 145 (4): 306–313. doi:10.1097/00005053-196710000-00005. PMID   6076017. S2CID   19328310.
  5. ↑ Martin WR, Sloan JW (1977). "Pharmacology and Classification of LSD-like Hallucinogens". In Martin WR (ed.). Drug Addiction II. Handbuch der experimentellen Pharmakologie. Handbook of Experimental Pharmacology. Vol. 45. Berlin, Heidelberg: Springer. pp. 305–368. doi:10.1007/978-3-642-66709-1_3. ISBN   978-3-642-66711-4.
  6. ↑ Blair JB, Kurrasch-Orbaugh D, Marona-Lewicka D, Cumbay MG, Watts VJ, Barker EL, Nichols DE (November 2000). "Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines". Journal of Medicinal Chemistry. 43 (24): 4701–4710. doi:10.1021/jm000339w. PMID   11101361.
  7. ↑ Rabin RA, Regina M, Doat M, Winter JC (May 2002). "5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens". Pharmacology, Biochemistry, and Behavior. 72 (1–2): 29–37. doi:10.1016/s0091-3057(01)00720-1. PMID   11900766. S2CID   6480715.
  8. ↑ Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN   978-3-662-55878-2. PMID   28401524.
  9. 1 2 Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, Vargas MV, McCarroll MN, Taylor JC, Myers-Turnbull D, Liu T, Yaghoobi B, Laskowski LJ, Anderson EI, Zhang G, Viswanathan J, Brown BM, Tjia M, Dunlap LE, Rabow ZT, Fiehn O, Wulff H, McCorvy JD, Lein PJ, Kokel D, Ron D, Peters J, Zuo Y, Olson DE (2021). "A non-hallucinogenic psychedelic analogue with therapeutic potential". Nature. 589 (7842): 474–479. doi:10.1038/s41586-020-3008-z. PMC   7874389 . PMID   33299186.
  10. ↑ Dong C, Ly C, Dunlap LE, Vargas MV, Sun J, Hwang IW, et al. (May 2021). "Psychedelic-inspired drug discovery using an engineered biosensor". Cell. 184 (10): 2779–2792.e18. doi:10.1016/j.cell.2021.03.043. PMC   8122087 . PMID   33915107.
  11. ↑ Glatfelter GC, Pottie E, Partilla JS, Stove CP, Baumann MH (2024). "Comparative pharmacological effects of lisuride and lysergic acid diethylamide revisited". ACS Pharmacology & Translational Science. 7 (3): 641–653. doi:10.1021/acsptsci.3c00274.
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