6-Fluorotryptamine

Last updated

6-Fluorotryptamine
6-Fluorotryptamine.svg
Clinical data
Other names6-Fluorotryptamine; 6-FT; 6-Fluoro-T; PAL-227; PAL227
Drug class Serotonin receptor agonist; Monoamine releasing agent; Monoamine oxidase inhibitor
Identifiers
  • 2-(6-fluoro-1H-indol-3-yl)ethanamine
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.215.037 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C10H11FN2
Molar mass 178.210 g·mol−1
3D model (JSmol)
  • C1=CC2=C(C=C1F)NC=C2CCN
  • InChI=1S/C10H11FN2/c11-8-1-2-9-7(3-4-12)6-13-10(9)5-8/h1-2,5-6,13H,3-4,12H2
  • Key:BQTOKMYKZPCPRW-UHFFFAOYSA-N

6-Fluorotryptamine (6-FT or 6-fluoro-T; code name PAL-227) is a serotonin receptor agonist and monoamine releasing agent (MRA) of the tryptamine family. [1] [2] [3]

Contents

Pharmacology

6-FT is known to have affinity for the serotonin 5-HT1A and 5-HT2A receptors, with Ki values of 267 nM and 606 nM, respectively. [4] [5] The drug is known to act as a full agonist of the serotonin 5-HT2A receptor, with an EC50 Tooltip half-maximal effective concentration of 4.56 nM and an Emax Tooltip maximal efficacy of 101%. [2] Another study found EC50 values of 54 nM at the serotonin 5-HT1A receptor and 81 nM at the serotonin 5-HT2A receptor. [5]

As an MRA, 6-FT is specifically a selective serotonin releasing agent (SRA). [2] It is one of the most potent SRAs known in vitro , with an EC50 Tooltip half-maximal effective concentration of 4.4 nM in rat brain synaptosomes. [2] It was more potent as an SRA than any other tryptamine in large series of compounds, and was second in potency of the assessed compounds only to the phenethylamine derivative naphthylaminopropane (NAP; PAL-287). [2] [6] 6-FT also much more weakly induces the release of dopamine and norepinephrine, with EC50 values of 106 nM (24-fold lower than serotonin) and 1,575 nM (358-fold lower than serotonin), respectively. [2]

Besides its serotonin receptor agonism and monoamine release induction, 6-FT is a somewhat potent monoamine oxidase inhibitor (MAOI), with IC50 Tooltip half-maximal inhibitory concentration values of 1,580 nM for monoamine oxidase A (MAO-A) and 5,620 nM for monoamine oxidase B (MAO-B). [1] [3]

In contrast to analogues like 6-fluoro-AMT and 6-fluoro-DMT as well as many other tryptamines, 6-FT fails to induce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. [1] [3] [5]

Tryptamines without substitutions at the amine or alpha carbon, such as tryptamine, serotonin (5-hydroxytryptamine; 5-HT), and 5-methoxytryptamine (5-MeO-T), are known to be very rapidly metabolized and thereby inactivated by monoamine oxidase A (MAO-A) in vivo and to have very short elimination half-lives. [7] [8] [9] [10] [11] [12] [13] However, given intravenously at sufficiently high doses, tryptamine is still known to be able to produce weak and short-lived psychoactive effects in humans. [14] [8] [2] [13]

History

6-FT was first described in the scientific literature by 1995. [1] [3]

See also

References

  1. 1 2 3 4 Nakagawasai O, Arai Y, Satoh SE, Satoh N, Neda M, Hozumi M, et al. (January 2004). "Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives". Neurotoxicology. 25 (1–2): 223–232. Bibcode:2004NeuTx..25..223N. doi:10.1016/S0161-813X(03)00101-3. PMID   14697897.
  2. 1 2 3 4 5 6 7 Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorg Med Chem Lett. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC   4211607 . PMID   25193229.
  3. 1 2 3 4 Tadano T, Neda M, Hozumi M, Yonezawa A, Arai Y, Fujita T, et al. (February 1995). "alpha-Methylated tryptamine derivatives induce a 5-HT receptor-mediated head-twitch response in mice". Neuropharmacology. 34 (2): 229–234. doi:10.1016/0028-3908(94)00119-d. PMID   7617148.
  4. ↑ 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.
  5. 1 2 3 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 10 March 2025
  6. ↑ Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology (Berl). 231 (21): 4135–4144. doi:10.1007/s00213-014-3557-7. PMC   4194234 . PMID   24800892.
  7. ↑ Jones RS (1982). "Tryptamine: a neuromodulator or neurotransmitter in mammalian brain?". Prog Neurobiol. 19 (1–2): 117–139. doi:10.1016/0301-0082(82)90023-5. PMID   6131482.
  8. 1 2 Shulgin A (1997). Tihkal: The Continuation. Transform Press. #53. T. ISBN   978-0-9630096-9-2 . Retrieved 17 August 2024. (with 250 mg, intravenously) "Tryptamine was infused intravenously over a period of up to 7.5 minutes. Physical changes included an increases in blood pressure, in the amplitude of the patellar reflex, and in pupillary diameter. The subjective changes are not unlike those seen with small doses of LSD. A point-by-point comparison between the tryptamine and LSD syndromes reveals a close similarity which is consistent with the hypothesis that tryptamine and LSD have a common mode of action."
  9. ↑ Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi: 10.1002/wmts.42 . ISSN   2190-460X.
  10. ↑ 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.
  11. ↑ Prozialeck WC, Vogel WH (February 1979). "MAO inhibition and the effects of centrally administered LSD, serotonin, and 5-methoxytryptamine on the conditioned avoidance response in rats". Psychopharmacology (Berl). 60 (3): 309–310. doi:10.1007/BF00426673. PMID   108709. In contrast, MAO inhibition greatly increased brain levels of 5-HT and 5-MT (Prozialeck and Vogel, 1978). For instance, clorgyline and deprenyl increased brain levels of 5-HT 8.5-fold and 4.4-fold and of 5-MT 20-fold and 5-fold, respectively.
  12. ↑ Boess FG, Martin IL (1994). "Molecular biology of 5-HT receptors". Neuropharmacology. 33 (3–4): 275–317. doi:10.1016/0028-3908(94)90059-0. PMID   7984267.
  13. 1 2 Martin WR, Sloan JW (1970). "Effects of infused tryptamine in man". Psychopharmacologia. 18 (3): 231–237. doi:10.1007/BF00412669. PMID   4922520.
  14. ↑ Martin WR, Sloan JW (1977). "Pharmacology and Classification of LSD-like Hallucinogens". Drug Addiction II. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 305–368. doi:10.1007/978-3-642-66709-1_3. ISBN   978-3-642-66711-4. MARTIN and SLOAN (1970) found that intravenously infused tryptamine increased blood pressure, dilated pupils, enhanced the patellar reflex, and produced perceptual distortions. [...] Tryptamine, but not DMT, increases locomotor activity in the mouse, while both antagonize reserpine depression (V ANE et al., 1961). [...] In the rat, tryptamine causes backward locomotion, Straub tail, bradypnea and dyspnea, and clonic convulsions (TEDESCHI et al., 1959). [...] Tryptamine produces a variety of changes in the cat causing signs of sympathetic activation including mydriasis, retraction of nictitating membrane, piloerection, motor signs such as extension of limbs and convulsions and affective changes such as hissing and snarling (LAIDLAW, 1912). [...]


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