5-Methoxytryptamine

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-selectiveserotonin receptor agonist;Serotonin5-HT2A receptoragonist;Serotonergic psychedelic;Hallucinogen
Pharmacokinetic data
Metabolism	MAO-ATooltip Monoamine oxidase A
Identifiers
IUPAC name 2-(5-Methoxy-1H-indol-3-yl)ethanamine
CAS Number	608-07-1 Y
PubChemCID	1833
IUPHAR/BPS	107
ChemSpider	1767 Y
UNII	3VMW6141KC
KEGG	C05659 Y
ChEBI	CHEBI:2089 Y
ChEMBL	ChEMBL8165 Y
CompTox Dashboard(EPA)	DTXSID60209638
ECHA InfoCard	100.009.231
Chemical and physical data
Formula	C11H14N2O
Molar mass	190.246 g·mol−1
3D model (JSmol)	Interactive image
SMILES O(c1cc2c(cc1)[nH]cc2CCN)C
InChI InChI=1S/C11H14N2O/c1-14-9-2-3-11-10(6-9)8(4-5-12)7-13-11/h2-3,6-7,13H,4-5,12H2,1H3 Y Key:JTEJPPKMYBDEMY-UHFFFAOYSA-N Y
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5-Methoxytryptamine (5-MT,5-MeO-T, or5-OMe-T), also known asserotonin methyl ether orO-methylserotonin and asmexamine, is atryptaminederivative closely related to theneurotransmittersserotonin andmelatonin.^[3] It has been shown tooccur naturally in the body in low levels, especially in thepineal gland.^[3][4] It is formed viaO-methylation of serotonin orN-deacetylation of melatonin.^[3][5][4]

5-MT is a highlypotent andnon-selectiveserotonin receptor agonist^[6][7][8][9] and showsserotonergic psychedelic-like effects in animals.^[10] However, it is inactive in humans, at leastorally, likely due to rapidmetabolism bymonoamine oxidase (MAO).^[1][2] The levels and effects of 5-MT are dramatically potentiated bymonoamine oxidase inhibitors (MAOIs) in animals.^{[11][12][13][14][15][16]}

5-MT can be formed byO-methylation ofserotonin mediated byhydroxyindoleO-methyltransferase (HIOMT) or byN-deacetylation of melatonin.^[3][5] It is also aprecursor of5-MeO-DMT in some species.^[3]

5-MT acts as anagonist of theserotonin5-HT₁,5-HT₂,5-HT₄,5-HT₆, and5-HT₇ receptors.^{[22][23][24][25][26][27][28][29]}

It is an extremelypotent serotonin5-HT_2A receptor agonistin vitro, with anEC₅₀Tooltip half-maximal effective concentration 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 anEC₅₀ of 3.87 nM (7.7-fold lower) anddimethyltryptamine (DMT) had anEC₅₀ of 38.3 nM (76-fold lower).[9]

5-MT has been said to be 25- and 400-foldselective for the serotonin5-HT_2B receptor over the serotonin 5-HT_2A and5-HT_2C receptors, respectively.^[30]

5-MT, in contrast to the closely relatedmelatonin, has noaffinity for themelatonin receptors.^[31][32] 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 amonoamine releasing agent compared totryptamine and serotonin.^[8]

5-MTdose-dependently induces thehead-twitch response, a behavioral proxy ofpsychedelic effects, in rodents, and this effect is reversed by serotonin 5-HT_2A receptorantagonists.^{[10][33][34][35][36][15][16]} As such, it may be ahallucinogen in humans.^[37] 5-MT is only briefly mentioned in several places inAlexander Shulgin'sTiHKAL and its psychoactive effects are not described.^[38][39] Besides psychedelic-like effects, 5-MT produces a "hyperactivity syndrome" in rodents.^[3][11][40] It produces various other effects in animals as well.^[3]

5-MT is able to cross theblood–brain barrier and enter thecentral nervous system withperipheral administration in animals.^[11] However, it has also been reported that 5-MT shows strongperipheral selectivity in animals comparable toserotonin andbufotenin and that its capacity to exertcentral effects is limited.^[41]

5-MT ismetabolized bydeamination bymonoamine oxidase (MAO), specificallymonoamine oxidase A (MAO-A) and to a much lesser extent bymonoamine oxidase B (MAO-B).^{[12][13][14][42]}

Brain levels of 5-MT following central administration of 5-MT in rats were potentiated by 20-fold by theMAO-A inhibitorclorgyline and by 5.5-fold by theMAO-B inhibitorselegiline.^[13][12] Similarly, levels ofserotonin andphenethylamine 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 theconditioned avoidance response test, are markedly enhanced by MAOIs, including by the dual MAO-A and MAO-B inhibitoriproniazid and by clorgyline and selegiline.^[13]

Similarly to rat findings,pineal gland levels ofendogenous 5-MT are dramatically elevated by the MAO-A inhibitor clorgyline and by the dual MAO-A and MAO-B inhibitorpargyline in hamsters, and plasma levels ofexogenous 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 inhibitortranylcypromine has been frequently used to potentiate the effects of 5-MT inanimal studies.^{[11][34][36][15][16]}

5-MT isorally inactive in humans presumably due to rapid metabolism by MAO-A.^[1][2]

Metabolites of 5-MT include5-methoxyindole-3-acetic acid (5-MIAA) and5-methoxytryptophol.^[3][14] It may also be metabolized intomelatonin.^[3][5]

5-MT, also known as 5-methoxytryptamine or as 5-hydroxytrypamineO-methyl ether, is asubstituted tryptamine and aderivative ofserotonin (5-hydroxytryptamine) andprecursor ofmelatonin (N-acetyl-5-methoxytryptamine).^[43]

The predictedlog P of 5-MT is 0.5 to 1.41.^[43][44][45]

5-MT is closely related to other 5-methoxylated tryptamines such as5-MeO-NMT,5-MeO-DMT,5-MeO-DPT,5-MeO-DiPT,5-MeO-MiPT,5-MeO-DALT, and5-MeO-AMT. 5-MeO-AMT isorally 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 notableanalogues of 5-MT includetryptamine,2-methyl-5-hydroxytryptamine,5-benzyloxytryptamine,5-carboxamidotryptamine,5-methyltryptamine,5-(nonyloxy)tryptamine,α-methyl-5-hydroxytryptamine,acetryptine (5-acetyltryptamine), andisamide (N-chloroacetyl-5-methoxytryptamine), among others.

• Substituted tryptamine
• Serotonin (5-hydroxytryptamine; 5-HT)
• N-Acetylserotonin
• Melatonin (5-methoxy-N-acetyltryptamine)

• 5-Methoxytryptamine - Isomer Design

• 5-HT1A agonists
• 5-HT2A agonists
• 5-HT2B agonists
• 5-HT2C agonists
• 5-HT4 agonists
• Human drug metabolites
• 5-Methoxytryptamines
• Peripherally selective drugs
• Psychedelic tryptamines
• Serotonin receptor agonists

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