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5-Fluoro-AMT

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5-Fluoro-AMT
Clinical data
Other names5-Fluoro-α-methyltryptamine; 5-Fluoro-alpha-methyltryptamine; 5-Fluoro-αMT; 5-Fluoro-AMT; 5F-AMT; PAL-212; PAL-544
Routes of
administration		Oral[1]
Drug classSerotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonin–norepinephrine–dopamine releasing agent; Serotonergic psychedelic; Hallucinogen; Stimulant; Entactogen
Identifiers
  • 1-(5-fluoro-1H-indol-3-yl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H13FN2
Molar mass192.237 g·mol−1
3D model (JSmol)
  • Fc1cc2c(cc1)[nH]cc2CC(N)C
  • InChI=1S/C11H13FN2/c1-7(13)4-8-6-14-11-3-2-9(12)5-10(8)11/h2-3,5-7,14H,4,13H2,1H3 checkY
  • Key:CTGFDWBZMCPVED-UHFFFAOYSA-N checkY
  (verify)

5-Fluoro-αMT, also known as 5-fluoro-α-methyltryptamine (5F-AMT) or as PAL-212[2][3] or PAL-544,[4][5] is a monoaminergic drug of the tryptamine and α-alkyltryptamine families related to α-methyltryptamine (αMT).[2][3][4]

The drug is known to act as a serotonin receptor agonist,[2][3] monoamine releasing agent,[2][3][4] and potent monoamine oxidase inhibitor.[6][7] It produces psychedelic- and stimulant-like effects in animals.[8][7][9][10] 5-Fluoro-AMT is also known to be psychoactive in humans, though its effects have not been described.[1]

5-Fluoro-AMT was first described in the scientific literature by 1963.[10] There has been interest in 5-fluoro-AMT as a possible treatment for cocaine dependence.[4]

Dosage and effects

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5-Fluoro-AMT has been said to be psychoactive in humans at a dose of 25 mg orally, although the qualitative nature of these effects has not been described.[1] Preclinical studies suggest that 5-fluoro-αMT may be a psychedelic, stimulant, and/or entactogen in humans.[2][3][4][8][7][9][10] However, 5-fluoro-AMT may be dangerous in humans due to its concomitant potent monoamine oxidase inhibition.[6][11]

Pharmacology

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5-Fluoro-AMT has been found to act as a fairly balanced serotonin-norepinephrine-dopamine releasing agent (SNDRA),[4][2] as a serotonin 5-HT2A receptor agonist,[2][12] and as a potent and specific MAO-A inhibitor.[11][13][14][15][16] Its EC50Tooltip half-maximal effective concentration values in terms of monoamine release are 14 to 19 nM for serotonin, 78 to 126 nM for norepinephrine, and 32 to 37 nM for dopamine in rat brain synaptosomes.[4][2][3] The drug's EC50 at the serotonin 5-HT2A receptor is 8.47 nM and its EmaxTooltip maximal efficacy at the receptor is 107%.[3] The IC50Tooltip half-maximal inhibitory concentration of 5-fluoro-AMT for MAO-A is 180 to 450 nM.[6][7][11] This is similar to the potency of αMT, para-methoxyamphetamine (PMA), and 4-methylthioamphetamine (4-MTA).[6]

5-Fluoro-αMT induces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents.[8][7][9] It is also known to reverse reserpine-induced behavioral depression, suggesting that it has antidepressant- or stimulant-like effects as well.[10] 5-Fluoro-AMT does not substitute for cocaine in drug discrimination tests but did substitute for cocaine in monkeys.[4] It does not facilitate intracranial self-stimulation (ICSS) in rodents.[4]

Chemistry

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Analogues of 5-fluoro-AMT include 5-fluorotryptamine, 5-fluoro-DMT, 5-fluoro-AET, and BK-5F-NM-AMT, as well as 5-chloro-αMT, 6-fluoro-AMT, 7-chloro-AMT, 7-methyl-αET, 5-API (PAL-571), and flucindole, among others. BK-5F-NM-AMT, the N-methyl and β-keto derivative of 5-fluoro-AMT, is a serotonin–dopamine releasing agent (SDRA) analogously to 5-fluoro-AMT.[17] In contrast to 5-fluoro-AMT and many other tryptamines however, BK-5F-NM-AMT is inactive as an agonist of serotonin receptors including the 5-HT1, 5-HT2, and 5-HT3 receptors and is inactive as a monoamine oxidase inhibitor (MAOI).[17]

History

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5-Fluoro-AMT was first described in the scientific literature by 1963 and was described as showing antidepressant- or stimulant-like effects in rodents.[10] It was first tried in humans by 1984.[1] The drug's psychedelic-like effects in animals were described by 1995,[9] 5-Fluoro-AMT's monoamine release and serotonin receptor agonism were shown by 2014, along with support for it having stimulant-like effects in monkeys.[2][3][4] The drug was investigated as a possible candidate for treatment of cocaine dependence and these findings were published in 2014.[4]

References

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  1. ^ a b c d McKenna DJ, Towers GH (1984). "Biochemistry and pharmacology of tryptamines and beta-carbolines. A minireview". J Psychoactive Drugs. 16 (4): 347–358. doi:10.1080/02791072.1984.10472305. PMID 6394730.
  2. ^ a b c d e f g h i 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.
  3. ^ a b c d e f g h Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, Rothman RB (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.
  4. ^ a b c d e f g h i j k Banks ML, Bauer CT, Blough BE, Rothman RB, Partilla JS, Baumann MH, Negus SS (June 2014). "Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys". Experimental and Clinical Psychopharmacology. 22 (3): 274–284. doi:10.1037/a0036595. PMC 4067459. PMID 24796848.
  5. ^ "5-Fluoro-AMT". Isomer Design. 11 November 2024. Retrieved 7 December 2024.
  6. ^ a b c d Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol. 10: 1590. doi:10.3389/fphar.2019.01590. PMC 6989591. PMID 32038257.
  7. ^ a b c d e Nakagawasai O, Arai Y, Satoh SE, Satoh N, Neda M, Hozumi M, Oka R, Hiraga H, Tadano T (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.
  8. ^ a b c Halberstadt AL, Geyer MA (2018). "Effect of Hallucinogens on Unconditioned Behavior". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 159–199. doi:10.1007/7854_2016_466. ISBN 978-3-662-55878-2. PMC 5787039. PMID 28224459.
  9. ^ a b c d Tadano T, Neda M, Hozumi M, Yonezawa A, Arai Y, Fujita T, Kinemuchi H, Kisara K (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.
  10. ^ a b c d e Kalir A, Szara S (November 1963). "Synthesis and Pharmacological Activity of Fluorinated Tryptamine Derivatives". J Med Chem. 6 (6): 716–719. doi:10.1021/jm00342a019. PMID 14184932.
  11. ^ a b c Wagmann L, Brandt SD, Kavanagh PV, Maurer HH, Meyer MR (April 2017). "In vitro monoamine oxidase inhibition potential of alpha-methyltryptamine analog new psychoactive substances for assessing possible toxic risks" (PDF). Toxicol Lett. 272: 84–93. doi:10.1016/j.toxlet.2017.03.007. PMID 28302559.
  12. ^ Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y (March 1998). "Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of mice". British Journal of Pharmacology. 123 (5): 855–862. doi:10.1038/sj.bjp.0701695. PMC 1565246. PMID 9535013.
  13. ^ Kinemuchi H, Arai Y (October 1986). "Selective inhibition of monoamine oxidase A and B by two substrate-analogues, 5-fluoro-alpha-methyltryptamine and p-chloro-beta-methylphenethylamine". Research Communications in Chemical Pathology and Pharmacology. 54 (1): 125–8. doi:10.1016/0028-3908(91)90057-i. PMID 3797802. S2CID 34761939.
  14. ^ Kim SK, Toyoshima Y, Arai Y, Kinemuchi H, Tadano T, Oyama K, et al. (April 1991). "Inhibition of monoamine oxidase by two substrate-analogues, with different preferences for 5-hydroxytryptamine neurons". Neuropharmacology. 30 (4): 329–35. doi:10.1016/0028-3908(91)90057-i. PMID 1852266. S2CID 34761939.
  15. ^ Corne SJ, Pickering RW (1967). "A possible correlation between drug-induced hallucinations in man and a behavioural response in mice". Psychopharmacologia. 11 (1): 65–78. doi:10.1007/bf00401509. PMID 5302272. S2CID 3148623.
  16. ^ Yamamoto T, Ueki S (January 1981). "The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs". Pharmacology, Biochemistry, and Behavior. 14 (1): 89–95. doi:10.1016/0091-3057(81)90108-8. PMID 6258178. S2CID 45561708.
  17. ^ a b WO 2022061242, Baggott M, "Advantageous tryptamine compositions for mental disorders or enhancement", published 2023 March 24, assigned to Tactogen 
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