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.
Unlike serotonin, αMS is not metabolized by monoamine oxidase on account of the α-methyl substituent blocking the enzyme access to the amine, and 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 mental effects.
α-Methyltryptophan (αMTP) is a prodrug to αMS which does cross the blood-brain-barrier and thus efficiently delivers αMS into the central nervous system. As a result, αMTP acts as an orally bioavailable false or substitute neurotransmitter for serotonin, and has been suggested as a therapeutic agent in the treatment of disorders where serotonin is deficient. The O-methylated analogue of αMS, 5-MeO-αMT, also readily enters the brain and may be used for this purpose as well.