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Substituted alpha-alkyltryptamine

α-Alkyltryptamines are a group of substituted tryptamines which possess an alkyl group, such as a methyl or ethyl group, attached at the alpha carbon, and in most cases no substitution on the amine nitrogen.[1][2][3] α-Alkylation of tryptamine makes it much more metabolically stable and resistant to degradation by monoamine oxidase, resulting in increased potency and greatly lengthened half-life.[3] This is analogous to α-methylation of phenethylamine into amphetamine.[3]

Many α-alkyltryptamines are drugs, acting as monoamine releasing agents, non-selective serotonin receptor agonists, and/or monoamine oxidase inhibitors,[4][5][6][7] and produce psychostimulant, entactogen, and/or psychedelic effects.[1][2][3] The most well-known of these agents are α-methyltryptamine (αMT) and α-ethyltryptamine (αET), both of which were used clinically as antidepressants for a brief period of time in the past and are abused as recreational drugs.[2][3] In accordance with its action as a dual releasing agent of serotonin and dopamine, αET has been found to produce serotonergic neurotoxicity similarly to amphetamines like MDMA and PCA, and the same is also likely to hold true for other serotonin and dopamine-releasing α-alkyltryptamines such as αMT, 5-MeO-αMT, and various others.[8]

List of substituted α-alkyltryptamines

Structure Common name Chemical name CAS number
AMT.svg αMT 1-(1H-Indol-3-yl)propan-2-amine 299-26-3
4-hydroxy-alphamethyltryptamine.png 4-HO-αMT 3-(2-aminopropyl)-1H-indol-4-ol 15066-09-8
4-Methyl-AMT.png 4-Methyl-αMT 1-methyl-2-(4-methyl-1H-indol-3-yl)-ethylamine 3569-29-7
5-fluoro-alpha-methyltryptamine.svg 5-Fluoro-αMT 1-(5-fluoro-1H-indol-3-yl)propan-2-amine 712-08-3
5-Chloro-3-(2-aminopropyl)indole.svg 5-Chloro-αMT 1-(5-Chloro-1H-indol-3-yl)propan-2-amine 712-07-2
5-HO-AMT structure.png 5-HO-αMT (αMS/α-methyl-5-HT) 3-(2-aminopropyl)-1H-indol-5-ol 304-52-9
5-MeO-AMT.svg 5-MeO-αMT 1-(5-methoxy-1H-indol-3-yl)propan-2-amine 1137-04-8
5EtO-AMT structure.png 5-Ethoxy-αMT 1-(5-ethoxy-1H-indol-3-yl)propan-2-amine 101832-83-1
6-fluoro-AMT structure.png 6-Fluoro-αMT 1-(6-fluoro-1H-indol-3-yl)propan-2-amine 712-11-8
A,N,O-TMS.png N-Methyl-5-MeO-αMT (α,N,O-TMS/α,N,O-trimethyl-5-HT) [1-(5-methoxy-1H-indol-3-yl)propan-2-yl](methyl)amine 4822-13-3
Α,N,N-TMT.png N,N-Dimethyl-αMT (α,N,N-TMT) (2-(1H-Indol-3-yl)-1-methyl-ethyl)dimethylamine
5MeO-TMT structure.png N,N-Dimethyl-5-MeO-αMT (5-MeO-α,N,N-TMT) (2-(5-methoxy-1H-Indol-3-yl)-1-methyl-ethyl)dimethylamine 101831-90-7
AMDIPT structure.png αMDiPT (2-(1H-Indol-3-yl)-1-methyl-ethyl)diisopropylamine
BW-723C86 structure.png BW-723C86 1-[5-(2-Thienylmethoxy)-1H-indol-3-yl]-2-propanamine 160521-72-2
AL-37350A structure.png AL-37350A (4,5-dihydropyrano-αMT) (S)-(+)-1-(2-Aminopropyl)-8,9-dihydropyrano[3,2-e]indole 362603-40-5
AET.svg αET 1-(1H-indol-3-yl)butan-2-amine 2235-90-7
4-Methyl-AET.png 4-Methyl-αET 1-(4-Methyl-1H-indol-3-yl)butan-2-amine 28289-30-7
4HO-AET structure.png 4-HO-αET 1-(4-hydroxy-1H-indol-3-yl)butan-2-amine 28289-28-3
5F-AET structure.png 5-Fluoro-αET 1-(5-fluoro-1H-indol-3-yl)butan-2-amine 1380137-98-3
5Me-AET structure.png 5-Methyl-αET 1-(5-methyl-1H-indol-3-yl)butan-2-amine 1380148-21-9
5-MeO-AET.svg 5-MeO-αET 1-(5-methoxy-1H-indol-3-yl)butan-2-amine 4765-10-0
7-Methyl-AET.png 7-Methyl-αET 1-(7-methyl-1H-indol-3-yl)butan-2-amine 13712-80-6
MPMI structure.png MPMI [9] 3-[(1-methylpyrrolidin-2-yl)methyl]-1H-indole 143321-54-4
4-HO-N-Me-TMT.png Lucigenol (R)-3-(N-methylpyrrolidin-2-ylmethyl)-4-hydoxyindole 250672-65-2
5-MeO-N-Me-TMT.svg 5-MeO-MPMI 5-Methoxy-3-{[(2R)-1-methylpyrrolidin-2-yl]methyl}-1H-indole 143321-57-7
5F-MPMI structure.png 5-F-MPMI 5-fluoro-3-[(1-methylpyrrolidin-2-yl)methyl]-1H-indole
5Br-MPMI structure.png 5-Br-MPMI 5-bromo-3-[(1-methylpyrrolidin-2-yl)methyl]-1H-indole 143322-57-0
Eletriptan skeletal.svg Eletriptan 3-{[(2R)-1-methylpyrrolidin-2-yl]methyl}-5-[2-(benzenesulfonyl)ethyl]-1H-indole 143322-58-1
Related compounds

A number of related compounds are known, with a similar structure but having the indole core flipped and/or replaced with related cores such as indoline, indazole or benzofuran. These similarly are primarily active as agonists at the 5-HT2 family of serotonin receptors, with applications in the treatment of glaucoma, cluster headaches or as anorectics.

Structure Common name Chemical name CAS number
3APB structure.png 3-APB 3-(2-aminopropyl)benzofuran 105909-13-5
Mebfap structure.png Mebfap 3-(2-aminopropyl)-5-methoxybenzofuran 140853-59-4
AL-34662 structure.png AL-34662 1-((S)-2-Aminopropyl)-1H-indazol-6-ol 210580-75-9
O-methyl-AL34662 structure.png O-methyl-AL-34662 1-((S)-6-methoxy-2-aminopropyl)-1H-indazole 210580-60-2
7-methyl-AL34662 structure.png 7-methyl-AL-34662 1-((S)-2-Aminopropyl)-7-methyl-1H-indazol-6-ol 874668-67-4
7-chloro-AL34662 structure.png 7-chloro-AL-34662 1-((S)-2-Aminopropyl)-7-chloro-1H-indazol-6-ol 874881-86-4
AL-38022A structure.png AL-38022A (S)-2-(8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl)-1-methylethylamine 478132-11-5
US6881749-9 structure.png Example 9 [10] (S)-α-methyl-pyrano[2,3-g]indazole-1(7H)-ethanamine 478132-12-6
US7425572-3 structure.png Example 3 [11] (S)-7,8-dihydro-α-methyl-1H-[1,4]dioxino[2,3-g]indazole-1-ethanamine 890087-75-9
US7268131-1 structure.png Example 1 [12] (S)-8,9-dihydro-α,9-dimethylpyrazolo[3,4-f][1,4]benzoxazine-1(7H)-ethanamine 1373917-69-1
Ro60-0175 structure.png Ro60-0175 (S)-(6-chloro-5-fluoro-1H-indol-1-yl)propan-2-amine 169675-09-6
VER-3323 structure.png VER-3323 (2S)-1-(6-bromo-2,3-dihydroindol-1-yl)propan-2-amine 259857-99-3
YM-348 structure.png YM-348 (2S)-1-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)propan-2-amine 372163-84-3
2-desethyl-YM348 structure.png 2-desethyl-YM-348 (2S)-1-(1H-furo[2,3-g]indazol-1-yl)propan-2-amine

See also

References

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  2. ^ a b c Laing RR (2003). Hallucinogens: A Forensic Drug Handbook. Academic Press. pp. 102–. ISBN 978-0-12-433951-4.
  3. ^ a b c d e Lemke TL, Williams DA (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 641–. ISBN 978-1-60913-345-0.
  4. ^ Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2–3): 132–7. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101.
  5. ^ Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, Rothman RB (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC 4211607. PMID 25193229.
  6. ^ Nonaka R, Nagai F, Ogata A, Satoh K (December 2007). "In vitro screening of psychoactive drugs by [(35)S]GTPgammaS binding in rat brain membranes". Biological & Pharmaceutical Bulletin. 30 (12): 2328–33. doi:10.1248/bpb.30.2328. PMID 18057721.
  7. ^ Feldman JM, Chapman B (December 1975). "Monoamine oxidase inhibitors: nature of their interaction with rabbit pancreatic islets to alter insluin secretion". Diabetologia. 11 (6): 487–94. doi:10.1007/bf01222097. PMID 1107123.
  8. ^ Huang XM, Johnson MP, Nichols DE (July 1991). "Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase)". European Journal of Pharmacology. 200 (1): 187–90. doi:10.1016/0014-2999(91)90686-K. PMID 1722753.
  9. ^ Macor JE, Wythes MJ. Indole derivatives. US patent 5607951
  10. ^ US granted 6881749, Chen HH, May JA, Severns BS, "Pyranoindazoles and their use for the treatment of glaucoma", published 3 June 2004, issued 19 April 2005, assigned to Alcon, Inc. 
  11. ^ US granted 7425572, Chen HH, May JA, "Use of dioxindoindazoles and dioxoloindazoles for treating glaucoma", published 8 June 2006, issued 16 September 2008, assigned to Alcon, Inc. 
  12. ^ US granted 7268131, Dantanarayana AP, May JA, "Substituted [1,4]oxazino[2,3-g]indazoles for the treatment of glaucoma", published 15 December 2005, issued 11 September 2007, assigned to Alcon, Inc. 

Further reading