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6-Fluorotryptamine

From Wikipedia, the free encyclopedia

Pharmaceutical compound
6-Fluorotryptamine
Clinical data
Other names6-Fluorotryptamine; 6-FT; 6-Fluoro-T; PAL-227; PAL227
Drug classSerotonin receptor agonist;Monoamine releasing agent;Monoamine oxidase inhibitor
Identifiers
  • 2-(6-fluoro-1H-indol-3-yl)ethanamine
CAS Number
PubChemCID
ChemSpider
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.215.037Edit this at Wikidata
Chemical and physical data
FormulaC10H11FN2
Molar mass178.210 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 or6-fluoro-T; code namePAL-227) is aserotonin receptoragonist andmonoamine releasing agent (MRA) of thetryptamine family.[1][2][3]

Pharmacology

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6-FT is known to haveaffinity for theserotonin5-HT1A and5-HT2A receptors, with Ki values of 267 nM and 606 nM, respectively.[4][5] The drug is known to act as afull agonist of the serotonin 5-HT2A receptor, with anEC50Tooltip half-maximal effective concentration of 4.56 nM and anEmaxTooltip maximal efficacy of 101%.[2] Another study foundEC50 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 aselectiveserotonin releasing agent (SRA).[2] It is one of the mostpotent SRAs knownin vitro, with anEC50Tooltip half-maximal effective concentration of 4.4 nM in rat brainsynaptosomes.[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 thephenethylaminederivativenaphthylaminopropane (NAP; PAL-287).[2][6] 6-FT also much more weakly induces the release ofdopamine andnorepinephrine, withEC50 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 potentmonoamine oxidase inhibitor (MAOI), withIC50Tooltip half-maximal inhibitory concentration values of 1,580 nM formonoamine oxidase A (MAO-A) and 5,620 nM formonoamine oxidase B (MAO-B).[1][3]

In contrast toanalogues like6-fluoro-AMT and6-fluoro-DMT as well as many other tryptamines, 6-FT fails to induce thehead-twitch response, a behavioral proxy ofpsychedelic effects, in rodents.[1][3][5]

Tryptamines without substitutions at theamine oralpha carbon, such astryptamine,serotonin (5-hydroxytryptamine; 5-HT), and5-methoxytryptamine (5-MeO-T), are known to be very rapidlymetabolized and thereby inactivated bymonoamine oxidase A (MAO-A)in vivo and to have very shortelimination half-lives.[7][8][9][10][11][12][13] However, givenintravenously at sufficiently high doses, tryptamine is still known to be able to produce weak and short-livedpsychoactive effects in humans.[14][8][2][13]

History

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

See also

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References

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  1. ^abcdNakagawasai 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. ^abcdefgBlough 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. ^abcdTadano 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. ^abcChen 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, retrieved10 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. ^abShulgin A (1997).Tihkal: The Continuation. Transform Press.#53. T.ISBN 978-0-9630096-9-2. Retrieved17 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. ^abMartin 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). [...]

External links

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DRAsTooltip Dopamine releasing agents
NRAsTooltip Norepinephrine releasing agents
SRAsTooltip Serotonin releasing agents
Others
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT37
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
Non-specific
AAADTooltip Aromatic L-amino acid decarboxylase
MAOTooltip Monoamine oxidase
Phenethylamines
(dopamine,epinephrine,
norepinephrine)
PAHTooltip Phenylalanine hydroxylase
THTooltip Tyrosine hydroxylase
DBHTooltip Dopamine beta-hydroxylase
PNMTTooltip Phenylethanolamine N-methyltransferase
COMTTooltip Catechol-O-methyl transferase
Tryptamines
(serotonin,melatonin)
TPHTooltip Tryptophan hydroxylase
AANATTooltip Serotonin N-acetyl transferase
ASMTTooltip Acetylserotonin O-methyltransferase
Histamine
HDCTooltip Histidine decarboxylase
HNMTTooltip Histamine N-methyltransferase
DAOTooltip Diamine oxidase
Tryptamines
4-Hydroxytryptamines
andesters/ethers
5-Hydroxy- and
5-methoxytryptamines
N-Acetyltryptamines
α-Alkyltryptamines
Cyclized tryptamines
Isotryptamines
Related compounds
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