Substituted tryptamine
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 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.Ring-unsubstituted tryptamines
4-Hydroxytryptamines
5-Hydroxytryptamines
5-Methoxytryptamines
α-Alkyltryptamines
Other tryptamines
Interactions
Pharmacology
Pharmacodynamics
| Compound | 5-HT1A | 5-HT1B | 5-HT1D | 5-HT1E | 5-HT2A | 5-HT2B | 5-HT2C | 5-HT3 | 5-HT5A | 5-HT6 | 5-HT7 | SERT |
| DMT | 269 | 447 | 117 | 380 | 380 | 112 | 257 | – | 2,090 | 275 | 69 | 2,400 |
| Psilocin | 372 | 191 | 98 | 339 | 200 | 25 | 245 | – | 447 | 79 | 87 | 2,570 |
| Psilocybin | 5,250 | – | 195 | – | 851 | 479 | 3,090 | – | – | 776 | – | – |
| 4-AcO-MALT | 977 | – | 871 | 417 | 692 | 25 | 631 | – | – | 661 | 794 | 3,090 |
| Bufotenin | 8.3 | 59 | 22 | 25 | 224 | 6.2 | 209 | 166 | 302 | 18 | 8.9 | 1,120 |
| 5-MeO-DMT | 10 | 91 | 21 | 575 | 200 | 15 | 490 | – | 589 | 25 | 4.4 | – |
| 5-MeO-DiPT | 170 | – | 871 | – | 324 | 46 | – | – | – | 2,190 | – | – |
| 5-MeO-DALT | 17 | 1,020 | 54 | 977 | 457 | 100 | 2,240 | – | – | 162 | 60 | 4,470 |
| 5-MeO-EiPT | 54 | 1,170 | 174 | – | 1,622 | 98 | – | – | – | 407 | 661 | 5,620 |
| LSD | 5.9 | 21 | 3.5 | 135 | 8.5 | 5.5 | 17 | – | 1.8 | 16 | 8.5 | – |
| Compound | 5-HT1A | 5-HT1B | 5-HT1D | 5-HT1E | 5-HT2A | 5-HT2B | 5-HT2C | 5-HT3 | 5-HT5A | 5-HT6 | 5-HT7 | SERT |
| DMT | >10,000 | >10,000 | 93 | 456 | 2,323 | 108 | 335 | >10,000 | 611 | 487 | 883 | 3,742 |
| DPT | 32 | 854 | 619 | 2,338 | 2,579 | 42 | 1,567 | >10,000 | 4,373 | 4,543 | 284 | 157 |
| DiPT | 121 | >10,000 | 3,742 | >10,000 | >10,000 | 399 | >10,000 | >10,000 | >10,000 | >10,000 | 3,423 | 1,258 |
| Psilocin | 63 | 305 | 19 | 44 | 340 | 4.7 | 141 | >10,000 | 70 | 72 | 72 | 852 |
| 5-MeO-DMT | 1.9 | 74 | 6.3 | 360 | 2,011 | 3,884 | 538 | >10,000 | 277 | 36 | 3.9 | 2,032 |
| 5-MeO-DiPT | 132 | 5,137 | 1,718 | >10,000 | >10,000 | 163 | >10,000 | >10,000 | >10,000 | >10,000 | 1,231 | 2,531 |
| 5-MeO-MiPT | 12 | 303 | 23 | 3,496 | 448 | 59 | 2,186 | >10,000 | 953 | 130 | 20 | 6,409 |
| 6-Fluoro-DMT | 393 | 218 | 55 | 461 | 866 | 30 | 674 | >10,000 | 961 | 26 | 41 | 145 |
| 5-MeO-2-TMT | 200 | >10,000 | 250 | 1,800 | >10,000 | ? | 4,020 | ? | 10,450 | 60 | 145 | >10,000 |
| EMDT | 170 | >10,000 | 290 | 520 | >10,000 | ? | 1,810 | ? | 4,620 | 16 | 300 | >10,000 |
| Ibogaine | >10,000 | >10,000 | >10,000 | ? | 14,142 | ? | >10,000 | >10,000 | ? | ? | ? | 549 |
| LSD | 7.3 | 3.9 | 7.8 | 93 | 11 | 30 | 31 | >10,000 | 9 | 6.9 | 6.6 | >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.
| Structure | Name | Chemical name | CAS # |
| Tryptophan | -2-amino-3-propanoic acid | 73-22-3 | |
| 5-Hydroxytryptophan | 2-amino-3-propanoic acid | 4350-09-8 | |
| αMT | 1-propan-2-amine | 299-26-3 | |
| 4-HO-αMT | 3--1H-indol-4-ol | 15066-09-8 | |
| 4-Methyl-αMT | 1-methyl-2--ethylamine | 3569-29-7 | |
| 5-Fluoro-αMT | 1-propan-2-amine | 712-08-3 | |
| 5-Chloro-αMT | 1-propan-2-amine | 712-07-2 | |
| 5-HO-αMT | 3--1H-indol-5-ol | 304-52-9 | |
| 5-MeO-αMT | 1-propan-2-amine | 1137-04-8 | |
| 5-Ethoxy-αMT | 1-propan-2-amine | 101832-83-1 | |
| 5-Isopropoxy-αMT | 1-propan-2-amine | ||
| 5-Allyloxy-αMT | 1-propan-2-amine | ||
| BW-723C86 | 1--2-propanamine | 160521-72-2 | |
| 6-Fluoro-αMT | 1-propan-2-amine | 712-11-8 | |
| 7-Chloro-AMT | 1-propan-2-amine | 711-99-9 | |
| AL-37350A | --1--8,9-dihydropyranoindole | 362603-40-5 | |
| Compound 5 | 1-propan-2-amine | ||
| αET | 1-butan-2-amine | 2235-90-7 | |
| 4-Methyl-αET | 1-butan-2-amine | 28289-30-7 | |
| 4-HO-αET | 1-butan-2-amine | 28289-28-3 | |
| 5-Fluoro-αET | 1-butan-2-amine | 1380137-98-3 | |
| 5-Methyl-αET | 1-butan-2-amine | 1380148-21-9 | |
| 5-MeO-αET | 1-butan-2-amine | 4765-10-0 | |
| 7-Methyl-αET | 1-butan-2-amine | 13712-80-6 | |
| α,N-DMT | 1--N-methylpropan-2-amine | 299-24-1 | |
| N,N-Dimethyl-αMT | dimethylamine | 4761-32-4 | |
| N-Hydroxy-AMT | N-hydroxylamine | 63-33-2 | |
| N-Methyl-5-MeO-αMT | amine | 4822-13-3 | |
| N,''N-Dimethyl-5-MeO-αMT | dimethylamine | 101831-90-7 | |
| α-Propyltryptamine | 1-pentan-2-amine | ||
| Indolylpropylaminopentane | 1--N''-propylpentan-2-amine | ||
| α-Methyl-DiPT | diisopropylamine | ||
| MPMI | 3--1H-indole | 143321-54-4 | |
| Lucigenol | -3--4-hydoxyindole | 250672-65-2 | |
| 5-MeO-MPMI | 5-Methoxy-3--1H-indole | 143321-57-7 | |
| 5F-MPMI | -5-fluoro-3--1H-indole | ||
| 5-Br-MPMI | 5-bromo-3--1H-indole | 143322-57-0 | |
| Eletriptan | 3--5--1H-indole | 143322-58-1 | |
| Z5247692566 | 4--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 |