Α-Methylserotonin

Use and effects

According to Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved), αMS is well-studied in preclinical research but has not been tested in humans.

Pharmacology

Pharmacodynamics

αMS is a non-selective and near-full agonist of the serotonin 5-HT2 receptors. It has similar affinity for the 5-HT2A, 5-HT2B, and 5-HT2C receptors. The drug is also a ligand of the serotonin 5-HT1 receptors with high affinity, including of the serotonin 5-HT1A, 5-HT1B, and 5-HT1D receptors (Ki = 40–150nM), but not of the serotonin 5-HT1E receptor (Ki 10,000nM). 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.

In contrast to DOI, and in spite of its potent serotonin 5-HT2A receptor agonism, αMS did not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rats. However, it was only assessed at a dose of up to 1mg/kg, which is around the maximally effective dose of DOI.

Pharmacokinetics

Unlike serotonin, αMS is not metabolized by monoamine oxidase on account of the α-methyl substituent blocking the enzyme's access to the amine. 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.

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).

Properties

The predicted log P (XLogP3) of αMS is 0.6.

Analogues

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 (α,O-dimethylserotonin; α,O-DMS), also readily enters the brain, and could be used for such purposes as well.

Society and culture

Legal status

Canada

αMS is not an explicitly nor implicitly controlled substance in Canada as of 2025.

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.

References

References

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2. (1997). "TiHKAL: The Continuation". Transform Press.
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5. (July 1969). "Effects of alpha-methyl-5-hydroxytryptophan and alpha-methyl-5-hydroxytryptamine on norepinephrine in mouse myocardium". Biochem Pharmacol.
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12. (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.
13. (October 1990). "Effects of the 5-HT1C/5-5-HT2 receptor agonists DOI and alpha-methyl-5-HT on plasma glucose and insulin levels in the rat". Eur J Pharmacol.
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20. [http://leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&URL=0800-0899/0893/0893.html Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL]