Chemistry:5-MeO-AMT

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Short description: Chemical compound

5-MeO-AMT
Clinical data
Other names5-MeO-AMT; 5-Methoxy-α-methyltryptamine; α,O-Dimethylserotonin; α,O-DMS; Alpha-O
Routes of
administration		Oral[1]
Drug classSerotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Legal status
Legal status
  • AU: S9 (Prohibited substance)
  • BR: F2
  • CA: Unscheduled
  • DE: NpSG (Industrial and scientific use only)
  • UK: Class A
  • US: The DEA considers 5-MeO-AMT a controlled substance analogue.[2]
  • Illegal in Sweden and Florida
Pharmacokinetic data
Duration of action12–18 hours[1]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
FormulaC12H16N2O
Molar mass204.273 g·mol−1
3D model (JSmol)
Melting point216 to 218 °C (421 to 424 °F)
  (verify)

5-MeO-αMT, also known as 5-methoxy-α-methyltryptamine or as α,O-dimethylserotonin (α,O-DMS or Alpha-O), is a psychedelic drug of the tryptamine, α-alkyltryptamine, and 5-methoxytryptamine families.[1] It is a derivative of α-methyltryptamine (αMT) and an analogue of 5-MeO-DMT.[1] The drug is said to be the most potent psychedelic of the simple indolealkylamines (i.e., tryptamines).[3] It is taken orally and is used at doses of 2 to 4 mg.[3][1]

Use and effects

5-MeO-AMT blotters.
Tabs of gelatin containing 5-MeO-AMT.

In his book TiHKAL (Tryptamines I Have Known and Loved), Alexander Shulgin lists the dose range of 5-MeO-AMT as 2.5 to 4.5 mg and its duration as 12 to 18 hours.[1] However, a wider dose range of 0.5 to 15 mg has also been reported.[4][5]

5-MeO-AMT has supposedly been sold as 4 mg tablets by the street name Alpha-O and taken as a recreational drug. Since the DEA arrests of the makers of a huge percentage of the United States' LSD in 2000, 5-MeO-AMT may have occasionally been sold under the guise of LSD in liquid, sugar cube, or blotter form, though this may be due to DEA reports of finding it on sugar cubes and blotters like LSD.[6][7]

Shulgin has described the effects of 5-MeO-AMT in TiHKAL.[1]

Overdose

If misrepresented as LSD, 5-MeO-AMT can be extremely dangerous; users may take a number of "hits" of 5-MeO-AMT, assuming that it is LSD. Unlike LSD, which is very safe in overdose, 5-MeO-AMT can be very harmful or fatal. Particularly sensitive individuals can experience symptoms of overdose at dosages in the normal (for most users) range — as low as 20 mg. This has led to at least a few hospitalizations and possibly more than one death.[8][9] It is likely that the overdose potential of the compound is due to its sympathomimetic effects, as the side effects noted in overdose cases include cardiac arrhythmia and seizure. It also seems that oral consumption is safer than insufflation. Gloria Discerni, 18, died after overdosing on a drug initially believed to be LSD. Authorities learned months later that the drug wasn't LSD but a "designer drug" identified as 5-MeO-AMT.[10]

Interactions

Pharmacology

Pharmacodynamics

5-MeO-AMT activities
Target Affinity (Ki, nM)
5-HT1A 46–194 (Ki)
680 (EC50)
101% (Emax)
5-HT1B 417 (rat)
5-HT2A 3.1–34 (Ki)
2–8.4 (EC50)
84% (Emax)
5-HT2B 4 (EC50)
5-HT2C 90
α1A >12,000
α2A 11,000
D1 >25,000
D2 >25,000
D3 >25,000
H1 >25,000
TAAR1 1,100 (Ki) (rat)
4,800 (Ki) (mouse)
>10,000 (EC50) (human)
SERT 8,270–12,000 (Ki)
1,980–17,000 (IC50)
460 (EC50)
NET >22,000 (Ki)
37,000–78,000 (IC50)
8,900 (EC50)
DAT >26,000 (Ki)
2,690–43,000 (IC50)
1,500 (EC50)
MAO-A 31,000 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [11][12][13][14][15][16][17]

5-MeO-AMT acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT1A, 5-HT2A, and 5-HT2B receptors, among others.[13][12] Its EC50 at the serotonin 5-HT2A receptor has been found to be 2 to 8.4 nM.[13][12] In relation to this, it is an extremely potent agonist of the serotonin 5-HT2A receptor in vitro, showing the highest potency of any other tryptamine assessed in one study.[12] Its potency in activating the serotonin 5-HT2A receptor was 38-fold higher than that of dimethyltryptamine (DMT) and 361-fold higher than that of psilocin in the same study.[12] It is also a highly potent agonist of the serotonin 5-HT2B receptor, with an EC50 of 4 nM.[12]

Whereas tryptamine, serotonin (5-hydroxytryptamine), and αMT show potent activity as monoamine releasing agents, including of serotonin, norepinephrine, and/or dopamine, the monoamine-releasing activity of 5-methoxylated tryptamine derivatives, like 5-methoxytryptamine, 5-MeO-NMT, and 5-MeO-DMT among others, is dramatically reduced or abolished.[18][19][20][14][13] Accordingly, whereas the EC50 values of αMT for induction of monoamine release are 22 to 68 nM for serotonin, 79 to 112 nM for norepinephrine, and 79 to 180 nM for dopamine, the EC50 values in the case of 5-MeO-AMT are 460 nM for serotonin, 8,900 nM for norepinephrine, and 1,500 nM for dopamine.[14][19][12] Similarly, it is of very low potency as a monoamine reuptake inhibitor (IC50 values >1,000 nM).[14][12] Considering the very high potency of 5-MeO-AMT in activating the serotonin 5-HT2A receptor, its weak activities as a monoamine releasing agent and reuptake inhibitor are of questionable significance.[14][19][12][13]

5-MeO-AMT is a weak monoamine oxidase A (MAO-A) inhibitor, with an IC50 of 31,000 nM.[21][16] For comparison, the IC50 of AMT for MAO-A inhibition was 380 nM (~82-fold more potent than 5-MeO-AMT)[21][16] and the IC50 values of amphetamine (and its enantiomers) for MAO-A inhibition have been reported to be 11,000 to 70,000 nM.[21]

5-MeO-AMT produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and this is reversed by the serotonin 5-HT2A receptor antagonist ketanserin.[22][5][23] It substitutes for other psychedelics such as DOM and LSD in animal drug discrimination tests, but does not substitute for entactogens like MDMA or psychostimulants like dextromethamphetamine or cocaine.[24][13] In contrast to other psychedelics, 5-MeO-AMT has been found to not fully substitute for other psychedelics including DOM, LSD, and dimethyltryptamine (DMT), but did partially generalize to LSD (67% responding).[13] This is analogous to findings with 5-MeO-DMT, which has a major serotonin 5-HT2A receptor-mediated component to its discriminative stimulus properties.[25][26][27] 5-MeO-AMT does not produce locomotor hyperactivity, behavioral sensitization, conditioned place preference, or self-administration, further indicating a lack of psychostimulant-like effects as well as misuse potential.[13][22] Instead, 5-MeO-AMT produces hypolocomotion.[13] 5-MeO-AMT is known to produce sympathomimetic effects, but these effects likely depend on serotonin 5-HT2A receptor activation rather than on monoamine release or reuptake inhibition.[12] Other serotonergic psychedelics are also well known to produce sympathomimetic effects.[28][29][30]

Chemistry

5-MeO-AMT, also known as 5-methoxy-α-methyltryptamine, is a substituted tryptamine derivative. It is a derivative of tryptamine (T), 5-methoxytryptamine (5-MeO-T or 5-MT), and α-methyltryptamine (AMT or αMT) and is an analogue of other tryptamines like α-methylserotonin (5-HO-AMT) and 5-MeO-DMT. Some derivatives of 5-MeO-AMT include α,N-dimethyl-5-methoxytryptamine (5-MeO-α-Me-NMT or α,N,O-TMS) and α,N,N-trimethyl-5-methoxytryptamine (5-MeO-α-Me-DMT or α,N,N,O-TMS). As noted by Alexander Shulgin, the α-methylated tryptamines can be seen at as the tryptamine homologues of the amphetamines (α-methylated phenethylamines).

Properties

5-MeO-AMT is soluble in water and ethanol but not in ether.[31]

Synthesis

The chemical synthesis of 5-MeO-AMT has been described.[1]

Analogues

Analogues of 5-MeO-AMT include α-methyltryptamine (AMT), 4-HO-AMT, α-methylserotonin (5-HO-AMT), 5-EtO-AMT, 5-AlO-AMT, 5-fluoro-AMT, 5-chloro-AMT, α,N,O-TMS (5-MeO-N-Me-AMT), α,N,N,O-TeMS (5-MeO-α,N,N-TMT), 5-MeO-DMT, 5-MeO-DPT, 5-MeO-DiPT, O-Methyl-AL-34662 (indazole-5-MeO-AMT), and zalsupindole ((R)-5-MeO-N,N-DiMe-isoAMT), among others.

History

5-MeO-AMT was first synthesized and described in the scientific literature in 1958.[32][31][33] Its psychedelic effects in humans were first observed in 1976 and were described by Alexander Shulgin and David E. Nichols and colleagues by 1978.[32][31][34]

Society and culture

Australia

5-MeO-AMT is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).[35] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[35]

Finland

5-MeO-AMT is scheduled in the "government decree on psychoactive substances banned from the consumer market".[36]

Sweden

Sveriges riksdags health ministry Statens folkhälsoinstitut classified 5-MeO-αMT as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Oct 1, 2004, in their regulation SFS 2004:696 listed as 5-metoxi-alfametyltryptamin (5-MeO-AMT), making it illegal to sell or possess.[37]

United Kingdom

5-MeO-αMT was made illegal in the United Kingdom as of 7 January 2015, along with 5-MeO-DALT. This was following the events of 10 June 2014 when the Advisory Council on the Misuse of Drugs recommended that 5-MeO-αMT be scheduled as a class A drug by updating the blanket ban clause on tryptamines.

United States

5-MeO-AMT is unscheduled at the federal level in the United States.[38] However, the DEA considers the chemical a controlled substance analogue.[2] The agency's opinion on this matter may change at any time.

Florida

5-MeO-AMT is a Schedule I controlled substance in the state of Florida, making it illegal to buy, sell, or possess.[39]

See also

  • Substituted α-alkyltryptamine

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Shulgin, Alexander; Shulgin, Ann (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. http://www.erowid.org/library/books_online/tihkal/tihkal.shtml. 
  2. ↑ 2.0 2.1 "5-MeO-AMT; Fast Facts". January 1, 2006. https://www.justice.gov/archive/ndic/pubs9/9576/index.htm. 
  3. ↑ 3.0 3.1 "Synthesis of trans-2-(indol-3-yl)cyclopropylamines: Rigid tryptamine analogues". 1994. https://www.proquest.com/docview/304131663. "Figure 5. Rigid Serotonin Receptor Ligands [...]" 
  4. ↑ "Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics". Int J Neuropsychopharmacol 21 (10): 926–931. October 2018. doi:10.1093/ijnp/pyy047. PMID 29850881. 
  5. ↑ 5.0 5.1 "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology 167. May 2020. doi:10.1016/j.neuropharm.2019.107933. PMID 31917152. PMC 9191653. http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf. "Table 4 Human potency data for selected hallucinogens. [...]". 
  6. ↑ "The Identification of 5-Methoxy-alpha-methyltryptamine (5-MeO-AMT)". Microgram Journal (Drug Enforcement Administration) 1. January–June 2003. https://www.justice.gov/dea/programs/forensicsci/microgram/journal071203/mj071203_pg1.html. Retrieved 2011-09-16. 
  7. ↑ "Police Reports of 5-MeO-AMT". Erowid Vault. http://www.erowid.org/chemicals/5meo_amt/5meo_amt_info2.shtml. 
  8. ↑ "Reported LSD-Related death was not LSD". Erowid Vault. July 2007. http://www.erowid.org/chemicals/lsd/lsd_media2.shtml. 
  9. ↑ "5-MeO-AMT Hospitalizations & Possible Deaths". Erowid Vault. January 2007. http://www.erowid.org/chemicals/5meo_amt/5meo_amt_info1.shtml. 
  10. ↑ "Charges dropped in drug death". The Spokesman-Review. 13 December 2006. http://www.spokesman.com/stories/2006/dec/13/charges-dropped-in-drug-death/. 
  11. ↑ "BindingDB BDBM50227458 CHEMBL2093088". Journal of Medicinal Chemistry 31 (7): 1406–1412. 1988. doi:10.1021/jm00402a026. PMID 3385733. https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50227458. Retrieved 29 November 2024. 
  12. ↑ 12.00 12.01 12.02 12.03 12.04 12.05 12.06 12.07 12.08 12.09 "Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens". European Neuropsychopharmacology 26 (8): 1327–1337. August 2016. doi:10.1016/j.euroneuro.2016.05.001. PMID 27216487. http://edoc.unibas.ch/53326/1/20170117174852_587e4af45b658.pdf. 
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 "Abuse liability profile of three substituted tryptamines". J Pharmacol Exp Ther 338 (1): 280–289. July 2011. doi:10.1124/jpet.111.179705. PMID 21474568. 
  14. ↑ 14.0 14.1 14.2 14.3 14.4 "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology 559 (2–3): 132–137. March 2007. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101. 
  15. ↑ "Structure-Activity Relationship and Evaluation of Phenethylamine and Tryptamine Derivatives for Affinity towards 5-Hydroxytryptamine Type 2A Receptor". Biomol Ther (Seoul) 31 (2): 176–182. March 2023. doi:10.4062/biomolther.2022.096. PMID 36224112. 
  16. ↑ 16.0 16.1 16.2 "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. 
  17. ↑ "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1". J Pharmacol Exp Ther 357 (1): 134–144. April 2016. doi:10.1124/jpet.115.229765. PMID 26791601. https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA. 
  18. ↑ "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. 
  19. ↑ 19.0 19.1 19.2 "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. 
  20. ↑ "Therapeutic potential of monoamine transporter substrates". Curr Top Med Chem 6 (17): 1845–1859. 2006. doi:10.2174/156802606778249766. PMID 17017961. 
  21. ↑ 21.0 21.1 21.2 "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol 10. 2019. doi:10.3389/fphar.2019.01590. PMID 32038257. 
  22. ↑ 22.0 22.1 "5-Methoxy-α-methyltryptamine (5-MeO-AMT), a tryptamine derivative, induces head-twitch responses in mice through the activation of serotonin receptor 2a in the prefrontal cortex". Behav Brain Res 359: 828–835. February 2019. doi:10.1016/j.bbr.2018.07.020. PMID 30053461. 
  23. ↑ "1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity". J Med Chem 49 (1): 318–328. January 2006. doi:10.1021/jm050663x. PMID 16392816. 
  24. ↑ "A comparison of the behavioral properties of (+/-)-, (-)-, and (+)-5-methoxy-alpha-methyltryptamine". Biol Psychiatry 18 (4): 493–498. April 1983. PMID 6860723. 
  25. ↑ "A narrative synthesis of research with 5-MeO-DMT". J Psychopharmacol 36 (3): 273–294. March 2022. doi:10.1177/02698811211050543. PMID 34666554. 
  26. ↑ "Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions". Curr Drug Metab 11 (8): 659–666. October 2010. doi:10.2174/138920010794233495. PMID 20942780. 
  27. ↑ "The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors". Pharmacol Biochem Behav 65 (1): 75–82. January 2000. doi:10.1016/s0091-3057(99)00178-1. PMID 10638639. 
  28. ↑ "Cardiovascular safety of psychedelic medicine: current status and future directions". Pharmacol Rep 75 (6): 1362–1380. December 2023. doi:10.1007/s43440-023-00539-4. PMID 37874530. 
  29. ↑ "Effects of hallucinogenic drugs on the human heart". Front Pharmacol 15. 2024. doi:10.3389/fphar.2024.1334218. PMID 38370480. 
  30. ↑ "Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants". Neuropsychopharmacology 48 (11): 1659–1667. October 2023. doi:10.1038/s41386-023-01607-2. PMID 37231080. 
  31. ↑ 31.0 31.1 31.2 "Profiles of Psychedelic Drugs: α-O-DMS". Journal of Psychedelic Drugs 11 (3): 247. 1979. doi:10.1080/02791072.1979.10472112. ISSN 0022-393X. https://bitnest.netfirms.com/external/10.1080/02791072.1979.10472112. 
  32. ↑ 32.0 32.1 "Characterization of Three New Psychotomimetics". The Psychopharmacology of Hallucinogens. Elsevier. 1978. pp. 74–83. doi:10.1016/b978-0-08-021938-7.50010-2. ISBN 978-0-08-021938-7. https://bitnest.netfirms.com/external/10.1016/B978-0-08-021938-7.50010-2. 
  33. ↑ "Derivati indolici. III. Preparazione di alpha-alchil e alpha-ariltriptamine" (in Italian). Farmaco Sci 13 (12): 893–910. 1958. PMID 13619730. 
  34. ↑ "5-Methoxy-α-Methyltryptamine (α,O-Dimethylserotonin), A Hallucinogenic Homolog of Serotonin". Biol Psychiatry 15 (2): 349–352. April 1980. PMID 7417623. https://bitnest.netfirms.com/external/Biol.Psychiatry/15.2.349. 
  35. ↑ 35.0 35.1 "Poisons Standard". Federal Register of Legislation. Australian Government. October 2015. https://www.comlaw.gov.au/Details/F2015L01534. 
  36. ↑ "Valtioneuvoston asetus kuluttajamarkkinoilta kielletyistä psykoaktiivisista aineista | 1130/2014 | Lainsäädäntö | Finlex". https://www.finlex.fi/fi/lainsaadanto/2014/1130. 
  37. ↑ "Förordning om ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor" (in Swedish). Swedish Code of Statutes. 19 August 2004. http://www.notisum.se/rnp/sls/sfs/20040696.pdf. 
  38. ↑ "§1308.11 Schedule I.". Diversion Control Division. Drug Enforcement Administration, U.S. Department of Justice. http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm. 
  39. ↑ "Chapter 893 - Drug Abuse Prevention and Control". Florida Statutes. http://leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&URL=0800-0899/0893/0893.html. 

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