5-Methoxytryptamine

5-Methoxytryptamine (5-MT, 5-MeO-T, or 5-OMe-T), also known as serotonin methyl ether or O-methylserotonin and as mexamine, is a tryptamine derivative closely related to the neurotransmitters serotonin and melatonin. It has been shown to occur naturally in the body in low levels, especially in the pineal gland. It is formed via O-methylation of serotonin or N-deacetylation of melatonin.

5-MT is a highly potent and non-selective serotonin receptor agonist and shows serotonergic psychedelic-like effects in animals. However, it is inactive in humans, at least orally, likely due to rapid metabolism by monoamine oxidase (MAO). The levels and effects of 5-MT are dramatically potentiated by monoamine oxidase inhibitors (MAOIs) in animals.

5-MT can be formed by O-methylation of serotonin mediated by hydroxyindole O-methyltransferase (HIOMT) or by N-deacetylation of melatonin. It is also a precursor of 5-MeO-DMT in some species.

5-MT acts as an agonist of the serotonin 5-HT₁, 5-HT₂, 5-HT₄, 5-HT₆, and 5-HT₇ receptors.

It is an extremely potent serotonin 5-HT_2A receptor agonist in vitro, with an EC₅₀Tooltip half-maximal effective concentration of 0.503 nM. This was more potent than any other tryptamine evaluated in two large series of compounds. For comparison, 5-MeO-DMT had an EC₅₀ of 3.87 nM (7.7-fold lower) and dimethyltryptamine (DMT) had an EC₅₀ of 38.3 nM (76-fold lower).

5-MT has been said to be 25- and 400-fold selective for the serotonin 5-HT_2B receptor over the serotonin 5-HT_2A and 5-HT_2C receptors, respectively.

5-MT, in contrast to the closely related melatonin, has no affinity for the melatonin receptors. However, it may be converted into melatonin in the body, and hence may indirectly act as a melatonin receptor agonist.

5-MT shows dramatically reduced activity as a monoamine releasing agent compared to tryptamine and serotonin.