Chemistry:5-Fluoro-AMT

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Short description: Psychedelic drug
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
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC11H13FN2
Molar mass192.237 g·mol−1
3D model (JSmol)
  (verify)

5-Fluoro-αMT, also known as 5-fluoro-α-methyltryptamine (5F-AMT) or by its developmental code names PAL-212[2][3] and PAL-544,[4][5] is a monoaminergic drug of the tryptamine and α-alkyltryptamine families related to α-methyltryptamine (αMT).[2][3][4] It is taken orally.[1][6]

The drug is known to act as a serotonin receptor agonist,[2][3] monoamine releasing agent,[2][3][4] and potent monoamine oxidase inhibitor.[7][8] It produces psychedelic- and stimulant-like effects in animals.[9][8][10][11] 5-Fluoro-AMT is also known to be psychoactive in humans, though its effects have not been well-described.[1][6]

5-Fluoro-AMT was first described in the scientific literature by 1963.[11] There has been interest in 5-fluoro-AMT as a possible treatment for cocaine dependence.[4]

Use and effects

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 well-described.[1][6] Preclinical studies suggest that 5-fluoro-αMT may be a psychedelic, stimulant, and/or entactogen in humans.[2][3][4][9][8][10][11] However, 5-fluoro-AMT may be dangerous in humans due to its concomitant potent monoamine oxidase inhibition.[7][12]

William Leonard Pickard has described his experiences with 5-fluoro-AMT, which he had synthesized along with 6-fluoro-AMT, in personal interviews.[6] According to Pickard, 5-fluoro-AMT had a duration of at minimum 9 hours and varied in length significantly.[6] The dose was 25 mg and above.[6] Pickard has said that 5-fluoro-AMT was not a "warm drug" but that he remained favorable to it.[6] Its effects included time dilation among others.[6] He said that it gave him the worst post-trip headaches he'd experienced from any psychedelic and they lasted up to 24 hours.[6]

Pickard has said that 5-fluoro-AMT is less potent and long-lasting than 6-fluoro-AMT.[6] The related drug AMT was one of Pickard's favorite psychedelics, and he said that he took it more than 50 times and experienced no negative side effects with it.[6]

Interactions

Pharmacology

Pharmacodynamics

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][13] and as a potent and specific MAO-A inhibitor.[12][14][15][16][17] Its EC50 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 Emax at the receptor is 107%.[3] The IC50 of 5-fluoro-AMT for MAO-A is 180 to 450 nM.[7][8][12] This is similar to the potency of αMT, para-methoxyamphetamine (PMA), and 4-methylthioamphetamine (4-MTA).[7]

5-Fluoro-αMT induces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents.[9][8][10] It is also known to reverse reserpine-induced behavioral depression, suggesting that it has antidepressant- or stimulant-like effects as well.[11] 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

Analogues

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.[18] 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).[18]

History

5-Fluoro-AMT was first described in the scientific literature, by Asher Kalir and Stephen Szara, by 1963, and was described as showing antidepressant- or stimulant-like effects in rodents.[11] It was first tried in humans by 1984.[1] The drug's psychedelic-like effects in animals were described by 1995.[10] 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]

See also

  • Substituted α-alkyltryptamine

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Biochemistry and pharmacology of tryptamines and beta-carbolines. A minireview". J Psychoactive Drugs 16 (4): 347–358. 1984. doi:10.1080/02791072.1984.10472305. PMID 6394730. https://bitnest.netfirms.com/external/10.1080/02791072.1984.10472305. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology (Berl) 231 (21): 4135–4144. October 2014. doi:10.1007/s00213-014-3557-7. PMID 24800892. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorg Med Chem Lett 24 (19): 4754–4758. October 2014. doi:10.1016/j.bmcl.2014.07.062. PMID 25193229. 
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 "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. June 2014. doi:10.1037/a0036595. PMID 24796848. 
  5. ↑ "5-Fluoro-AMT". 11 November 2024. https://isomerdesign.com/pihkal/explore/5104. 
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 "Unusual Analogues: Drugs Used by Gordon Todd Skinner". This Land Press. http://thislandpress.com/2013/07/25/unusual-analogues-drugs-used-by-gordon-todd-skinner/. 
  7. ↑ 7.0 7.1 7.2 7.3 "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol 10. 2019. doi:10.3389/fphar.2019.01590. PMID 32038257. 
  8. ↑ 8.0 8.1 8.2 8.3 8.4 "Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives". Neurotoxicology 25 (1–2): 223–232. January 2004. doi:10.1016/S0161-813X(03)00101-3. PMID 14697897. Bibcode: 2004NeuTx..25..223N. 
  9. ↑ 9.0 9.1 9.2 "Effect of Hallucinogens on Unconditioned Behavior". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. 36. 2018. pp. 159–199. doi:10.1007/7854_2016_466. ISBN 978-3-662-55878-2. 
  10. ↑ 10.0 10.1 10.2 10.3 "alpha-Methylated tryptamine derivatives induce a 5-HT receptor-mediated head-twitch response in mice". Neuropharmacology 34 (2): 229–234. February 1995. doi:10.1016/0028-3908(94)00119-d. PMID 7617148. 
  11. ↑ 11.0 11.1 11.2 11.3 11.4 "Synthesis and Pharmacological Activity of Fluorinated Tryptamine Derivatives". J Med Chem 6 (6): 716–719. November 1963. doi:10.1021/jm00342a019. PMID 14184932. https://bitnest.netfirms.com/external/10.1021/jm00342a019. 
  12. ↑ 12.0 12.1 12.2 "In vitro monoamine oxidase inhibition potential of alpha-methyltryptamine analog new psychoactive substances for assessing possible toxic risks". Toxicol Lett 272: 84–93. April 2017. doi:10.1016/j.toxlet.2017.03.007. PMID 28302559. https://researchonline.ljmu.ac.uk/id/eprint/5909/1/TOXLET-D-17-00086R1_accepted_uncorected.pdf. 
  13. ↑ "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. March 1998. doi:10.1038/sj.bjp.0701695. PMID 9535013. 
  14. ↑ "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. October 1986. doi:10.1016/0028-3908(91)90057-i. PMID 3797802. 
  15. ↑ "Inhibition of monoamine oxidase by two substrate-analogues, with different preferences for 5-hydroxytryptamine neurons". Neuropharmacology 30 (4): 329–35. April 1991. doi:10.1016/0028-3908(91)90057-i. PMID 1852266. 
  16. ↑ "A possible correlation between drug-induced hallucinations in man and a behavioural response in mice". Psychopharmacologia 11 (1): 65–78. 1967. doi:10.1007/bf00401509. PMID 5302272. 
  17. ↑ "The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs". Pharmacology, Biochemistry, and Behavior 14 (1): 89–95. January 1981. doi:10.1016/0091-3057(81)90108-8. PMID 6258178. 
  18. ↑ 18.0 18.1 Baggott M, "Advantageous tryptamine compositions for mental disorders or enhancement", WO patent 2022061242, published 2023 March 24, assigned to Tactogen

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