Loading AI tools
Chemical compound From Wikipedia, the free encyclopedia
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.[3] It has been shown to occur naturally in the body in low levels, especially in the pineal gland.[3][4] It is formed via O-methylation of serotonin or N-deacetylation of melatonin.[3][5][4]
| |
| Clinical data | |
|---|---|
| Other names | 5-MeO-T; 5-OMe-T; 5-MeOT; 5-MeO-TPA; 5-MT; MT; 5-Hydroxytryptamine methyl ether; Serotonin methyl ether; O-Methylserotonin; O-Methyl-5-HT; Mexamine; Meksamin; Mekasamin; PAL-234 |
| Routes of administration | Orally inactive[1][2] |
| Drug class | Non-selective serotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen |
| Pharmacokinetic data | |
| Metabolism | MAO-A |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.009.231 |
| Chemical and physical data | |
| Formula | C11H14N2O |
| Molar mass | 190.246 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
| (verify) | |
5-MT is a highly potent and non-selective serotonin receptor agonist[6][7][8][9] and shows serotonergic psychedelic-like effects in animals.[10] However, it is inactive in humans, at least orally, likely due to rapid metabolism by monoamine oxidase (MAO).[1][2] The levels and effects of 5-MT are dramatically potentiated by monoamine oxidase inhibitors (MAOIs) in animals.[11][12][13][14][15][16]
5-MT can be formed by O-methylation of serotonin mediated by hydroxyindole O-methyltransferase (HIOMT) or by N-deacetylation of melatonin.[3][5] It is also a precursor of 5-MeO-DMT in some species.[3]
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 3.2 (Ki) 183–535 (EC50 66–135% (Emax) |
| 5-HT1B | 0.75–38 |
| 5-HT1D | 1.7–34 |
| 5-HT1E | 3,151 |
| 5-HT1F | 1,166 |
| 5-HT2A | 4.8–724 (Ki) 0.503 (EC50) 119% (Emax) |
| 5-HT2B | 0.51–16 |
| 5-HT2C | 45–943 |
| 5-HT3 | >10,000 (non-human) |
| 5-HT4 | 27–2,443 |
| 5-HT5A | 98 (unknown) |
| 5-HT6 | 18–88 |
| 5-HT7 | 0.5–5.0 |
| MT1 | >10,000 |
| MT2 | >10,000 |
| SERT | 4,000 (IC50) 2,169 (EC50) |
| NET | >10,000 (IC50) >10,000 (EC50) |
| DAT | >10,000 (IC50) 11,031 (EC50) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [6][7][8][9][17] | |
5-MT acts as an agonist of the serotonin 5-HT1, 5-HT2, 5-HT4, 5-HT6, and 5-HT7 receptors.[18][19][20][21][22][23][24]
It is an extremely potent serotonin 5-HT2A receptor agonist in vitro, with an EC50 of 0.503 nM.[8] This was more potent than any other tryptamine evaluated in two 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 to be 25- and 400-fold selective for the serotonin 5-HT2B receptor over the serotonin 5-HT2A and 5-HT2C receptors, respectively.[25]
5-MT, in contrast to the closely related melatonin, has no affinity for the melatonin receptors.[26][27] However, it may 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]
5-MT dose-dependently induces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and this effect is reversed by serotonin 5-HT2A receptor antagonists.[10][28][29][30][31][15][16] As such, it may be a hallucinogen in humans.[32] 5-MT is only briefly mentioned in several places in Alexander Shulgin's TiHKAL and its psychoactive effects are not described.[33][34] Besides psychedelic-like effects, 5-MT produces a "hyperactivity syndrome" in rodents.[3][11][35] It produces various other effects in animals as well.[3]
5-MT is able to cross the blood–brain barrier and enter the central nervous system with peripheral administration in animals.[11]
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).[12][13][14][36]
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.[13][12] Similarly, levels of serotonin and phenethylamine were also greatly elevated by these drugs.[12][13] 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 and by clorgyline and selegiline.[13]
Similarly to 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.[14] Conversely, selegiline was ineffective in elevating brain or plasma 5-MT levels in hamsters.[14]
The non-selective MAO-A and MAO-B inhibitor tranylcypromine has been frequently used to potentiate the effects of 5-MT in animal studies.[11][29][31][15][16]
5-MT is orally inactive in humans presumably due to rapid metabolism by MAO-A.[1][2]
Metabolites of 5-MT include 5-methoxyindole-3-acetic acid (5-MIAA) and 5-methoxytryptophol.[3][14] It may also be metabolized into melatonin.[3][5]
5-MT, also known as 5-methoxytryptamine or as 5-hydroxytrypamine O-methyl ether, is a substituted tryptamine and a derivative of serotonin (5-hydroxytryptamine) and precursor of melatonin (N-acetyl-5-methoxytryptamine).[37]
It is closely related to other 5-methoxylated tryptamines such as 5-MeO-NMT, 5-MeO-DMT, 5-MeO-DPT, 5-MeO-DiPT, 5-MeO-MiPT, 5-MeO-DALT, and 5-MeO-AMT. 5-MeO-AMT is orally active in humans, in contrast to 5-MT, and could be thought of as a sort of orally active form of 5-MT.[2] Some other notable analogues of 5-MT include tryptamine, 2-methyl-5-hydroxytryptamine, 5-benzyloxytryptamine, 5-carboxamidotryptamine, 5-(nonyloxy)tryptamine, α-methyl-5-hydroxytryptamine, acetryptine (5-acetyltryptamine), and isamide (N-chloroacetyl-5-methoxytryptamine), among others.
Seamless Wikipedia browsing. On steroids.
Every time you click a link to Wikipedia, Wiktionary or Wikiquote in your browser's search results, it will show the modern Wikiwand interface.
Wikiwand extension is a five stars, simple, with minimum permission required to keep your browsing private, safe and transparent.
