5-Methoxytryptamine

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5-MT acts as an agonist of the serotonin 5-HT₁, 5-HT₂, 5-HT₄, 5-HT₆, and 5-HT₇ receptors.^{[40][41][42][43][44][45][46][47]} Conversely, it is completely devoid of activity at the serotonin 5-HT₃ receptor.^[48][49]

The drug is an extremely potent serotonin 5-HT_2A receptor agonist in vitro, with an EC₅₀Tooltip half-maximal effective concentration of 0.5 nM in one study.^[8] This was more potent than any other tryptamine evaluated in a large series of compounds.^[8][9] 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).^[9]

5-MT has been said in the past 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.^[50] Conversely however, a more modern study found EC₅₀ values for activation of G_αq signaling of 2.6 nM at the serotonin 5-HT_2A receptor, 0.7 nM at the serotonin 5-HT_2B receptor, and 0.1 nM at the serotonin 5-HT_2C receptor, indicating preference for the serotonin 5-HT_2C receptor rather than for the serotonin 5-HT_2B receptor.^[38]

The drug has been found to show substantially higher affinity for the serotonin 5-HT_1A receptor than tryptamine or DMT (K_i = 6.1 nM, 125 nM, and 245 nM, respectively; 20- to 40-fold higher affinity).^[51] On the other hand, it shows slightly lower affinity for this receptor than serotonin but a little more than twice the affinity of 5-MeO-DMT (K_i = 3.2 nM, 1.7 nM, and 7.8 nM, respectively).^[52]

5-MT, in contrast to the closely related melatonin, has no affinity for the melatonin receptors.^[53][54] Conversely, in Tango assay at a concentration of 10 μM, it displayed agonist-like activity at the melatonin MT₁ receptor.^[38] The drug may also be converted into melatonin in the body, and hence may indirectly act as a melatonin receptor agonist.^[3][5]

5-MT shows dramatically reduced activity as a monoamine releasing agent compared to tryptamine and serotonin.^[8]

Effects

Both tryptamine and 5-MT failed to substitute for 5-MeO-DMT in rodent drug discrimination tests.^[10][55][11] Instead, only behavioral disruption occurred, which it was theorized might be a peripherally mediated effect.^[10][55][11]

On the other hand, 5-MT dose-dependently induces the head-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents, and this effect is reversed by serotonin 5-HT_2A receptor antagonists.^{[13][19][20][56][57][58][59]} As such, it may theoretically be hallucinogenic in humans.^[60] However, in a couple of other more recent studies, 5-MT failed to produce the HTR, instead inducing only serotonin 5-HT_1A receptor-mediated hypothermia and hypolocomotion.^[38][61][62] In one of these studies, the ED₅₀Tooltip effective dose (pharmacology) of 5-MT in producing the HTR was greater than 30 mg/kg, whereas the ED₅₀ of 5-MeO-DMT was 0.33 mg/kg, an at least 91-fold difference in dose.^[38] Conversely, the drug was 2.8-fold more potent than 5-MeO-DMT in producing hypolocomotion and was only slightly less potent than 5-MeO-DMT in producing hypothermia.^[38] Co-administration of the serotonin 5-HT_1A receptor antagonist WAY-100635 did not unmask an HTR with 5-MT, similarly to the case of 5-MeO-NMT but in contrast to the case of 5-MeO-NET.^[38] It was hypothesized that reduced blood–brain barrier permeability with drugs like 5-MT might be involved in these findings.^[38]

Besides the preceding effects, 5-MT produces a "hyperactivity syndrome" in rodents.^[3][15][63] It produces various other effects in animals as well.^[3] 5-MT has been reported to produce weak psychedelic-like behavioral effects in monkeys at relatively high doses of 10 to 20 mg/kg.^[10][11][12] The drug has also been studied as a possible LSD antagonist in rodents.^[14][64]

Absorption

5-MT is said to be orally inactive in humans presumably due to rapid metabolism by monoamine oxidase (MAO).^[1][2]

Distribution

5-MT is able to cross the blood–brain barrier and enter the central nervous system with peripheral administration in animals.^[15] However, it has also been reported that 5-MT shows strong peripheral selectivity in animals comparable to serotonin and bufotenin and that its capacity to exert central effects is limited.^{[10][11][65][66]}

Metabolism

5-MT is metabolized by deamination by monoamine oxidase (MAO), specifically monoamine oxidase A (MAO-A) and to a much lesser extent by monoamine oxidase B (MAO-B).^{[16][17][18][67]} Metabolites of 5-MT include 5-methoxyindole-3-acetic acid (5-MIAA) and 5-methoxytryptophol.^[3][18] It may also be metabolized into melatonin.^[3][5]

Brain levels of 5-MT following central administration of 5-MT in rats were potentiated by 20-fold by the MAO-A inhibitor clorgyline and by 5.5-fold by the MAO-B inhibitor selegiline.^[17][16] Similarly, levels of serotonin and phenethylamine were also greatly elevated by these drugs.^[16][17] In accordance with the potentiation of brain levels of 5-MT by MAOIs, the behavioral effects of centrally administered 5-MT in rats, for instance in the conditioned avoidance response test, are markedly enhanced by MAOIs, including by the dual MAO-A and MAO-B inhibitor iproniazid as well as by clorgyline and selegiline.^[17] The non-selective MAO-A and MAO-B inhibitor tranylcypromine has also been frequently used to potentiate the effects of 5-MT in animal studies.^{[15][57][59][19][20]} Similarly to the exogenous rat findings, pineal gland levels of endogenous 5-MT are dramatically elevated by the MAO-A inhibitor clorgyline and by the dual MAO-A and MAO-B inhibitor pargyline in hamsters, and plasma levels of exogenous 5-MT are greatly elevated by these MAOIs as well.^[18] Conversely, selegiline was ineffective in elevating brain or plasma 5-MT levels in hamsters.^[18]

Canada

5-MT is not a controlled substance in Canada as of 2025.^[80]

United states

5-MT is not an explicitly controlled substance in the United States.^[81] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.