Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine 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 (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) 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 (from "psilocybin mushrooms") 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 (Tryptamines I Have Known and Loved).
Use and effects The doses, potencies, durations, and effects of psychedelic tryptamines have been reviewed by Alexander Shulgin and other authors.
Ring-unsubstituted tryptamines
4-Hydroxytryptamines
5-Hydroxytryptamines
5-Methoxytryptamines
α-Alkyltryptamines
Other tryptamines
Interactions
Pharmacology
Pharmacodynamics
Chemistry
Synthesis The chemical syntheses of numerous tryptamines have been described by Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved). 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. The chemical syntheses of the psychedelic tryptamines bufotenin (5-HO-DMT) and 5-MeO-DMT (mebufotenin) have been comprehensively reviewed.
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 (AMT) and α-ethyltryptamine (AET), 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, AET 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 AMT, 5-MeO-AMT, and various others.
List of substituted β-ketotryptamines A number of β-ketotryptamines (beta-ketotryptamines) are known. These compounds are α-alkyl-β-ketotryptamines and are analogous to the cathinones (β-ketoamphetamines) 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:
β-Carbolines such as harmala alkaloids like harmaline Ibogalogs (hexahydroazepinoindoles) such as ibogainalog, tabernanthalog, PNU-22394, and PHA-57378 Iboga alkaloids like ibogaine, noribogaine, ibogamine, and tabernanthine Ergolines and lysergamides such as lysergic acid diethylamide (LSD) and ergot alkaloids like ergine (lysergic acid amide; LSA) Partial ergolines and lysergamides like RU-27849, FHATHBIN, NDTDI, and CT-5252 Mitragyna alkaloids such as mitragynine Yohimbans such as Rauvolfia and Corynanthe alkaloids like yohimbine and rauwolscine Pyrrolidinylethylindoles like pyr-T, 4-HO-pyr-T, 5-MeO-pyr-T, 4-F-5-MeO-pyr-T, and L-760790 Pyrrolidinylmethylindoles like MPMI, 4-HO-MPMI (lucigenol), 5F-MPMI, 5-MeO-MPMI, CP-135807, eletriptan, and MSP-2020 Imidazolylindoles like AGH-107, AGH-192, and AH-494 Piperidinylethylindoles like pip-T, 5-MeO-pip-T, and indoramin Morpholinylethylindoles like mor-T and 5-MeO-mor-T Tetrahydropyridinylindoles like RS134-49 (4-Me-THPI), RU-28253 (5-MeO-THPI), and NEtPhOH-THPI Pertines (phenylpiperazinylethylindoles) like alpertine, milipertine, oxypertine, and solypertine Tetrahydrocarbazolamines like ciclindole, flucindole, frovatriptan, LY-344864, and ramatroban Tetrahydropyrroloquinolines like bufothionine, O-methylnordehydrobufotenine, and dehydrobufotenine Others like 5-MeO-IsoqT, barettin, cyclic 3-hydroxymelatonin, metralindole, and Z5247692566 Other closely related cyclized tryptamine-like compounds include the following:
Piperidinylindoles like SN-22, BRL-54443, naratriptan, LY-334370, and sertindole Tetrahydropyridinylindoles like RU-24969, EMD-386088, and LY-367,265 Tetrahydropyridinylindazoles like VU6067416 Tetrahydropyridinylpyrrolopyridines like (R)-69, (R)-70, CP-93129, and CP-94253 Pyridopyrroloquinoxalines (tetracyclic γ-carbolines) like lumateperone, IHCH-7113, IHCH-7086, and ITI-1549
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