Tryptamines

Tryptamines, specifically substituted tryptamines, are organic compounds built upon a core tryptamine backbone. This fundamental structure consists of an indole ring and an amine group connected by an ethyl sidechain. Substituents can be located at the amine, on the indole ring, or along the sidechain.

This broad class of substances includes neurotransmitters like serotonin, alongside numerous alkaloids found in plants and fungi, such as psilocybin, bufotenine, DMT, and mescaline. Ann and Alexander Shulgin extensively researched and documented many novel compounds within this class in their book TiHKAL. More complex compounds like LSD, yohimbine, and mitragynine are technically tryptamines. Most psychoactive tryptamines have psychedelic, empathogenic and to a lesser extend stimulating effects.

Ring and Amine Substituted Tryptamines

Amine Substitutions

Substituents at the amine are typically alkyl groups, starting with methyl groups. There are usually two substituents at the amine. Interestingly, DMT, with two methyl groups at the amine, is orally inactive. However, MET, which has one methyl and one ethyl group, is orally active, as are other tryptamines with larger alkyl substituents at the amine.

Indole Ring Substitutions

The most common substituents on the indole ring are hydroxy and acetoxy groups at the 4th carbon, and methoxy groups as well as halogen substituents at the 5th carbon.

It's widely believed that 4-AcO-Tryptamines are at least partially prodrugs to their 4-HO-Tryptamine equivalents. In contrast, 5-HO-Tryptamines and 6-HO-Tryptamines, like bufotenin (5-HO-DMT), are either inactive or less active than their 4-HO counterparts. This difference in activity may be due to 5-HO-Tryptamines being more hydrophilic than 4-HO-Tryptamines, which makes it harder for them to cross the blood-brain barrier. Similarly, 4-, 6-, and 7-MeO-Tryptamines also appear to be inactive.

Regarding halogenation, tryptamines with halogens at the 5th position are active, whereas those halogenated at the 4th and 6th positions do not seem to be.

α- and β-substituted Tryptamines

α-alkylated Tryptamines

α-alkylated tryptamines, such as αMT and αET, are active substances that tend to be more empathogenic and stimulating compared to their non-α-substituted counterparts. While simpler amine and ring substituted tryptamines typically act as serotonin receptor agonists, α-alkylated tryptamines function as monoamine oxidase inhibitors (MAOIs) and monoamine releasing agents. This difference in mechanism accounts for their distinct subjective effects.

β-substituted Tryptamines

Most β substituted tryptamines are β-ketones. β-ketone tryptamines are analogues to cathinones (β-ketone-phenethylamines). They are neither serotonin agonists nor MAOIs; instead, they act as monoamine releasing agents. Some of these compounds are selective serotonin-dopamine releasing agents, being very weak norepinephrine releasers.

Complex Substituted Tryptamines

More complex compounds like Iboga alkaloids, β-carbolines, ergolines (including LSD), and mitragyna alkaloids technically contain the tryptamine structure as part of their larger molecules. These compounds are incredibly diverse can not be categorised easily. For example, mitragyna alkaloids act on opioid receptors, making them atypical opioids.