Misplaced Pages

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
PubChem CID	2107
IUPHAR/BPS	152
ChemSpider	2023
UNII	5Y83TBC5NM
ChEBI	CHEBI:48295
ChEMBL	ChEMBL275854
CompTox Dashboard (EPA)	DTXSID10657549
Chemical and physical data
Formula	C11H14N2O
Molar mass	190.246 g·mol
3D model (JSmol)	Interactive image
SMILES c2cc(O)cc1c2cc1CC(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 Key:LYPCGXKCQDYTFV-UHFFFAOYSA-N
(verify)

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.

Pharmacology

αMS is a non-selective and near-full agonist of the serotonin 5-HT₂ receptors. It has similar affinity for the 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors. 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). 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.

Unlike serotonin, αMS is not metabolized by monoamine oxidase on account of the α-methyl substituent blocking the enzyme's access to the amine. As a result, it has a much longer half-life in comparison. Similarly to serotonin however, αMS poorly crosses the blood-brain-barrier due to its free hydroxyl group, and thus has only weak or no central effects when administered peripherally.

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.

Legal status

United States

αMS is not scheduled at the federal level in the United States, 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.

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. 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. The O-methylated analogue of αMS, 5-MeO-αMT, also readily enters the brain, and could be used for such purposes as well.

See also

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

References

1. ^ Ismaiel AM, Titeler M, Miller KJ, Smith TS, Glennon RA (February 1990). "5-HT1 and 5-HT2 binding profiles of the serotonergic agents alpha-methylserotonin and 2-methylserotonin". Journal of Medicinal Chemistry. 33 (2): 755–8. doi:10.1021/jm00164a046. PMID 2299641.
2. ^ Maroteaux L, Ayme-Dietrich E, Aubertin-Kirch G, Banas S, Quentin E, Lawson R, Monassier L (February 2017). "New therapeutic opportunities for 5-HT2 receptor ligands". Pharmacol Ther. 170: 14–36. doi:10.1016/j.pharmthera.2016.10.008. PMID 27771435. alpha-methyl-5-HT is a non-selective nearly full agonist at 5-HT2 receptors with similar affinity to 5-HT2A 5-HT2B and 5-HT2C receptors (Jerman, et al., 2001; Knight, et al., 2004; Porter, et al., 1999).
3. Lahti RA, Platz PA, Heinzelman RV (July 1969). "Effects of alpha-methyl-5-hydroxytryptophan and alpha-methyl-5-hydroxytryptamine on norepinephrine in mouse myocardium". Biochem Pharmacol. 18 (7): 1601–1608. doi:10.1016/0006-2952(69)90147-6. PMID 5306701.
4. Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology (Berl). 231 (21): 4135–4144. doi:10.1007/s00213-014-3557-7. PMC 4194234. PMID 24800892.
5. Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, Rothman RB (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC 4211607. PMID 25193229.
6. ^ "Erowid Online Books : "TIHKAL" - #48 a-MT".
7. Diksic M, Nagahiro S, Sourkes TL, Yamamoto YL (January 1990). "A new method to measure brain serotonin synthesis in vivo. I. Theory and basic data for a biological model". Journal of Cerebral Blood Flow and Metabolism. 10 (1): 1–12. doi:10.1038/jcbfm.1990.2. PMID 2298826.
8. "3-(2-aminopropyl)-1H-indol-5-ol". PubChem. Retrieved 7 October 2024.
9. "§1308.11 Schedule I." Archived from the original on 2009-08-27. Retrieved 2014-12-17.
10. Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL
11. ^ Sourkes TL, Montine TJ, Missala K (1990). "Alpha-methylserotonin, a substitute transmitter for serotonergic neurons". Progress in Neuro-psychopharmacology & Biological Psychiatry. 14 (5): 829–32. doi:10.1016/0278-5846(90)90055-l. PMID 1705718. S2CID 25604266.
12. ^ Sourkes TL (1991). "Alpha-methyltryptophan as a therapeutic agent". Progress in Neuro-psychopharmacology & Biological Psychiatry. 15 (6): 935–8. doi:10.1016/0278-5846(91)90020-2. PMID 1763198. S2CID 31504647.
13. "Erowid Online Books : "TIHKAL" - #5. a,O-DMS".

• Drugs not assigned an ATC code
• 5-HT2A agonists
• 5-HT2B agonists
• 5-HT2C agonists
• Alpha-Alkyltryptamines
• Hydroxyarenes
• Non-hallucinogenic 5-HT2A receptor agonists
• Norepinephrine releasing agents
• Peripherally selective drugs
• Psychedelic tryptamines
• Serotonin receptor agonists