Α-Methylserotonin

α-Methylserotonin (αMS), also known as α-methyl-5-hydroxytryptamine (α-methyl-5-HT) or 5-hydroxy-α-methyltryptamine (5-HO-αMT), is a tryptamine derivative closely related to the neurotransmitter serotonin (5-HT). It acts as a non-selective serotonin receptor agonist and has been used extensively in scientific research to study the function of the serotonin system.^[1]

α-Methylserotonin

Clinical data
Routes of administration	Oral
ATC code	none
Legal status
Legal status	Uncontrolled (but may be covered under the Federal Analogue Act in the United States and under similar bills in other countries)
Identifiers
IUPAC name 3-(2-aminopropyl)-1H-indol-5-ol
CAS Number	304-52-9 Y
PubChem CID	2107
IUPHAR/BPS	152
ChemSpider	2023 Y
UNII	5Y83TBC5NM
ChEBI	CHEBI:48295 Y
ChEMBL	ChEMBL275854 Y
CompTox Dashboard (EPA)	DTXSID10657549
Chemical and physical data
Formula	C11H14N2O
Molar mass	190.246 g·mol−1
3D model (JSmol)	Interactive image
SMILES c2cc(O)cc1c2[nH]cc1CC(N)C
InChI InChI=1S/C11H14N2O/c1-7(12)4-8-6-13-11-3-2-9(14)5-10(8)11/h2-3,5-7,13-14H,4,12H2,1H3 Y Key:LYPCGXKCQDYTFV-UHFFFAOYSA-N Y
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Use and effects

According to Alexander Shulgin in TiHKAL, αMS is well-studied in preclinical research but has not been tested in humans.^[2]

Pharmacology

αMS is a non-selective and near-full agonist of the serotonin 5-HT₂ receptors.^[3][4] It has similar affinity for the 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors.^[3] The drug is also a ligand of the serotonin 5-HT₁ receptors with high affinity, including of the serotonin 5-HT_1A, 5-HT_1B, and 5-HT_1D receptors (K_i = 40–150 nM), but not of the serotonin 5-HT_1E receptor (K_i > 10,000 nM).^[1] In addition to its actions at the serotonin receptors, αMS has been found to act as a norepinephrine releasing agent similarly to α-methylphenylalanine and to other α-alkylated tryptamines.^[5][6][7]

Unlike serotonin, αMS is not metabolized by monoamine oxidase on account of the α-methyl substituent blocking the enzyme's access to the amine.^[8][9][10] Similarly to serotonin however, αMS poorly crosses the blood–brain barrier due to its free hydroxyl group and poor lipophilicity, and thus may have weak or no central effects when administered peripherally.^[8][11]

In contrast to DOI, and in spite of its potent serotonin 5-HT_2A receptor agonism, αMS did not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rats.^[12] However, it was only assessed at a dose of up to 1 mg/kg,^[12] which is around the maximally effective dose of DOI.^[13]

Chemistry

αMS, also known as α-methyl-5-hydroxytryptamine (α-methyl-5-HT), is a substituted tryptamine derivative and the α-methylated analogue of serotonin (5-hydroxytryptamine or 5-HT).

The predicted log P (XLogP3) of αMS is 0.6.^[14]

Legal status

United States

αMS is not scheduled at the federal level in the United States,^[15] but it could be considered an analogue of α-methyltryptamine (AMT), in which case, purchase, sales, or possession could be prosecuted under the Federal Analog Act.

Florida

αMS is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in Florida.^[16]

Other drugs

α-Methyltryptophan (αMTP) and α-methyl-5-hydroxytryptophan (α-Me-5-HTP) are prodrugs of αMS which cross the blood–brain barrier and thus efficiently deliver αMS into the central nervous system.^[17][18] As a result, these compounds act as orally bioavailable false or substitute neurotransmitters for serotonin, and have been suggested as possible therapeutic agents in the treatment of disorders where serotonin is deficient.^[17][18] The O-methylated analogue of αMS, 5-MeO-αMT (α,O-dimethylserotonin; α,O-DMS), also readily enters the brain, and could be used for such purposes as well.^[8][19]

See also

• 2-Methyl-5-hydroxytryptamine
• 5-Carboxamidotryptamine
• 5-Methoxytryptamine
• α-Methyldopamine