Substituted tryptamine


[Image:Tryptamine rests General Formula V.svg|thumb|right|200px|class=skin-invert-image|The structure of substituted tryptamines. Tryptamine itself is obtained when R4=R5=RN1=RN2=Rα = H.]
[Image:Tryptamine structure.svg|thumb|right|225px|class=skin-invert-image|The structure of substituted tryptamines with all positions labeled.]
Substituted tryptamines, or simply tryptamines, also known as serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring system, joined to an amino (NH2) group via an ethyl sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen atoms.
Well-known tryptamines include serotonin, an important neurotransmitter, and melatonin, a hormone involved in regulating the sleep-wake cycle. Tryptamine alkaloids are found in fungi, plants and animals; and sometimes used by humans for the neurological or psychotropic effects of the substance. Prominent examples of tryptamine alkaloids include psilocybin and DMT. In South America, dimethyltryptamine is obtained from numerous plant sources, like chacruna, and it is often used in ayahuasca brews. Many synthetic tryptamines have also been made, including the migraine drug sumatriptan, and psychedelic drugs. A 2022 study has found the variety of tryptamines present in wild mushrooms may affect the therapeutic impact.
The tryptamine structure, in particular its indole ring, may be part of the structure of some more complex compounds, for example cyclized tryptamines like LSD, ibogaine, harmaline, mitragynine and yohimbine. A thorough investigation of dozens of tryptamine compounds was published by Alexander Shulgin and Ann Shulgin in 1997 under the title TiHKAL.

Use and effects

The doses, potencies, durations, and effects of psychedelic tryptamines have been reviewed by Alexander Shulgin and other authors.

Pharmacology

Pharmacodynamics

Compound5-HT1A5-HT1B5-HT1D5-HT1E5-HT2A5-HT2B5-HT2C5-HT35-HT5A5-HT65-HT7SERT
DMT269447117380380112257–2,090275692,400
Psilocin3721919833920025245–44779872,570
Psilocybin5,250–195–8514793,090––776––
4-AcO-MALT977–87141769225631––6617943,090
Bufotenin8.35922252246.2209166302188.91,120
5-MeO-DMT10912157520015490–589254.4–
5-MeO-DiPT170–871–32446–––2,190––
5-MeO-DALT171,020549774571002,240––162604,470
5-MeO-EiPT541,170174–1,62298–––4076615,620
LSD5.9213.51358.55.517–1.8168.5–

Compound5-HT1A5-HT1B5-HT1D5-HT1E5-HT2A5-HT2B5-HT2C5-HT35-HT5A5-HT65-HT7SERT
DMT>10,000>10,000934562,323108335>10,0006114878833,742
DPT328546192,3382,579421,567>10,0004,3734,543284157
DiPT121>10,0003,742>10,000>10,000399>10,000>10,000>10,000>10,0003,4231,258
Psilocin6330519443404.7141>10,000707272852
5-MeO-DMT1.9746.33602,0113,884538>10,000277363.92,032
5-MeO-DiPT1325,1371,718>10,000>10,000163>10,000>10,000>10,000>10,0001,2312,531
5-MeO-MiPT12303233,496448592,186>10,000953130206,409
6-Fluoro-DMT3932185546186630674>10,0009612641145
5-MeO-2-TMT200>10,0002501,800>10,000?4,020?10,45060145>10,000
EMDT170>10,000290520>10,000?1,810?4,62016300>10,000
Ibogaine>10,000>10,000>10,000?14,142?>10,000>10,000???549
LSD7.33.97.893113031>10,00096.96.6>10,000

Chemistry

Synthesis

The chemical syntheses of numerous tryptamines have been described by Alexander Shulgin in his book TiHKAL. A well-known and widely used synthetic approach for making tryptamines is the Speeter–Anthony route, which starts with indole. Other tryptamine synthesis routes have also been described, for instance starting with tryptamine rather than indole.

List of substituted tryptamines

List of substituted α-alkyltryptamines

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. 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. This is analogous to α-methylation of phenethylamine into amphetamine.
Many α-alkyltryptamines are drugs, acting as monoamine releasing agents, non-selective serotonin receptor agonists, and/or monoamine oxidase inhibitors, and produce psychostimulant, entactogen, and/or psychedelic effects. The most well-known of these agents are α-methyltryptamine and α-ethyltryptamine, both of which were used clinically as antidepressants for a brief period of time in the past and are abused as recreational drugs. 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.
StructureNameChemical nameCAS #
Tryptophan-2-amino-3-propanoic acid73-22-3
5-Hydroxytryptophan 2-amino-3-propanoic acid4350-09-8
αMT 1-propan-2-amine299-26-3
4-HO-αMT3--1H-indol-4-ol15066-09-8
4-Methyl-αMT1-methyl-2--ethylamine3569-29-7
5-Fluoro-αMT1-propan-2-amine712-08-3
5-Chloro-αMT1-propan-2-amine712-07-2
5-HO-αMT 3--1H-indol-5-ol304-52-9
5-MeO-αMT1-propan-2-amine1137-04-8
5-Ethoxy-αMT1-propan-2-amine101832-83-1
5-Isopropoxy-αMT1-propan-2-amine
5-Allyloxy-αMT1-propan-2-amine
BW-723C861--2-propanamine160521-72-2
6-Fluoro-αMT1-propan-2-amine712-11-8
7-Chloro-AMT1-propan-2-amine711-99-9
AL-37350A --1--8,9-dihydropyranoindole362603-40-5
Compound 51-propan-2-amine
αET1-butan-2-amine2235-90-7
4-Methyl-αET1-butan-2-amine28289-30-7
4-HO-αET1-butan-2-amine28289-28-3
5-Fluoro-αET1-butan-2-amine1380137-98-3
5-Methyl-αET1-butan-2-amine1380148-21-9
5-MeO-αET1-butan-2-amine4765-10-0
7-Methyl-αET1-butan-2-amine13712-80-6
α,N-DMT 1--N-methylpropan-2-amine299-24-1
N,N-Dimethyl-αMT dimethylamine4761-32-4
N-Hydroxy-AMT N-hydroxylamine63-33-2
N-Methyl-5-MeO-αMT amine4822-13-3
N,''N-Dimethyl-5-MeO-αMT dimethylamine101831-90-7
α-Propyltryptamine 1-pentan-2-amine
Indolylpropylaminopentane 1--N''-propylpentan-2-amine
α-Methyl-DiPTdiisopropylamine
MPMI3--1H-indole143321-54-4
Lucigenol -3--4-hydoxyindole250672-65-2
5-MeO-MPMI 5-Methoxy-3--1H-indole143321-57-7
5F-MPMI-5-fluoro-3--1H-indole
5-Br-MPMI5-bromo-3--1H-indole143322-57-0
Eletriptan3--5--1H-indole143322-58-1
Z52476925664--3-morpholine
BK-NM-AMT 1--2-propan-1-one
BK-5F-NM-AMT 1--2-propan-1-one
BK-5Cl-NM-AMT 1--2-propan-1-one
BK-5Br-NM-AMT 1--2-propan-1-one

List of substituted β-ketotryptamines

A number of β-ketotryptamines are known. These compounds are α-alkyl-β-ketotryptamines and are analogous to the cathinones of the related phenethylamine family. Known β-ketotryptamines include BK-NM-AMT, BK-5F-NM-AMT, BK-5Cl-NM-AMT, and BK-5Br-NM-AMT. They act as monoamine releasing agents.

Cyclized tryptamines

Examples of cyclized tryptamines include:
Other closely related cyclized tryptamine-like compounds include the following:

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 indene, indoline, indazole, indolizine, benzothiophene, or benzofuran. Like tryptamines, these related compounds 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.
StructureNameChemical nameCAS #
C-DMT 2--N,''N-dimethylethanamine
O-DMT 2--N'',N-dimethylethanamine
MiPBF N--N-methylpropan-2-amine
Dimemebfe 2--N,''N-dimethylethanamine140853-58-3
5-MeO-DiBF N''--N-propan-2-amine
3-APB 3-benzofuran105909-13-5
Mebfap 3--5-methoxybenzofuran140853-59-4
S-DMT 2--N,''N-dimethylethanamine10275-64-6
3-APBT 1-propan-2-amine1201-27-0
Isotryptamine 2-indol-1-ylethanamine13708-58-2
isoAMT1-indol-1-ylpropan-2-amine1227465-67-9
-5,6-Difluoro-isoAMT-1-propan-2-amine
Ro60-0175 -propan-2-amine169675-09-6
isoDMT2-indol-1-yl-N,N-dimethylethanamine87482-09-5
5-MeO-isoDMT2--N,N-dimethylethanamine244122-80-3
6-MeO-isoDMT2--N,N-dimethylethanamine87482-11-9
Zalsupindole -1--N,N-dimethylpropan-2-amine2481740-94-5
2ZEDMA2-indolizin-1-yl-N'',N-dimethylethanamine
1ZP2MA1-indolizin-1-yl-N-methylpropan-2-amine
1Z2MAP1O1-indolizin-3-yl-2-propan-1-one2110204-31-2
Example 161--N,N-dimethylpropan-2-amine
Example 11-propan-2-amine
VER-3323-1-propan-2-amine259857-99-3
AL-34662 1--1H-indazol-6-ol210580-75-9
O-Methyl-AL-34662 1--1H-indazole210580-60-2
7-Methyl-AL-346621--7-methyl-1H-indazol-6-ol874668-67-4
7-Chloro-AL-346621--7-chloro-1H-indazol-6-ol874881-86-4
AL-38022A-2--1-methylethylamine478132-11-5
Example 9-α-methyl-pyranoindazole-1-ethanamine478132-12-6
Example 3-7,8-dihydro-α-methyl-1H-dioxinoindazole-1-ethanamine890087-75-9
Example 1-8,9-dihydro-α,9-dimethylpyrazolobenzoxazine-1-ethanamine1373917-69-1
YM-348-1-propan-2-amine372163-84-3
2-Desethyl-YM-348-1-propan-2-amine748116-94-1
I-323--1H-indol-4-ol
2-Azapsilocin 3--1H-indazol-4-ol
4-Aza-5-MeO-DPT N--N-propylpropan-1-amine
5-Aza-4-MeO-DiPT N--N-propan-2-amine
7-Aza-5-MeO-DiPT N--N-propan-2-amine
RS134-49 4-methyl-3--1H-indole2945139-94-4
RU-28253 5-methoxy-3--1H-indole
NEtPhOH-THPI 3--1H-indole
VU60674163--5-bromo-1H-indazole3027515-24-5
(R)-693--1H-pyrrolopyridine2765652-48-8
SN-223--1H-indole17403-07-5
RU-24,9695-methoxy-3--1H-indole107008-28-6
EMD-3860885-chloro-2-methyl-3--1H-indole54635-62-0