Α-Methylmelatonin Explained

α-Methylmelatonin, also known as α-methyl-5-methoxy-N-acetyltryptamine, is a synthetic tryptamine derivative and analogue of the monoamine neurotransmitter melatonin.^[1] It is a metabolite of α-methyltryptophan, α-methyl-5-hydroxytryptophan, and α-methylserotonin that can be formed in small amounts via aralkylamine N-acetyltransferase (AANAT).^[2] α-Methyltryptophan and α-methyl-5-hydroxytryptophan are prodrugs of α-methylserotonin that have serotonergic actions and have been suggested for potential therapeutic use.^{[3] [4] [5] [6]} However, while formation of α-methylmelatonin can occur from these compounds, α-alkylated tryptamines show 95% reduced suitability as substrates for AANAT compared to non-α-alkylated tryptamines in vitro and no α-methylmelatonin could be detected with administration of α-methyltryptophan in vivo in animals. α-Methyl-N-acetylserotonin is an intermediate is the formation of α-methylmelatonin from α-methylserotonin.^[7]

Notes and References

1. Montine TJ, Missala K, Sourkes TL . Alpha-methyltryptophan metabolism in rat pineal gland and brain . J Pineal Res . 12 . 1 . 43–48 . January 1992 . 1564632 . 10.1111/j.1600-079x.1992.tb00024.x .
2. Montine TJ, Missala K, Sourkes TL . Alpha-methyltryptophan metabolism in rat pineal gland and brain . J Pineal Res . 12 . 1 . 43–48 . January 1992 . 1564632 . 10.1111/j.1600-079x.1992.tb00024.x .
3. Sourkes TL . Alpha-methyltryptophan as a therapeutic agent . Prog Neuropsychopharmacol Biol Psychiatry . 15 . 6 . 935–938 . 1991 . 1763198 . 10.1016/0278-5846(91)90020-2 .
4. Diksic M, Young SN . Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan . J Neurochem . 78 . 6 . 1185–1200 . September 2001 . 11579128 . 10.1046/j.1471-4159.2001.00536.x .
5. Sourkes TL . Conversion of alpha-methyltryptophan to alpha-methylserotonin in vivo. New techniques for imaging serotonin . Adv Neurol . 60 . 515–518 . 1993 . 8420181 .
6. Diksic M, Grdisa M . Alpha-methyl-L-tryptophan as a tracer to study brain serotonergic system . Neurochem Res . 20 . 11 . 1353–1360 . November 1995 . 8786822 . 10.1007/BF00992511 .
7. Web site: CID 54262547 . PubChem . 8 October 2024.