Melatonin Is Metabolized to JV-Acetyl Serotonin and 6-Hydroxymelatonin in Man

Abstract

To investigate whether melatonin (_aMT) can be metabolized to N-acetyl serotonin (NAS), a low dose of deuter-ated _aMT was administered to four normal subjects, and their urine samples were analyzed for the presence of deuterated NAS and deuterated 6-hydroxymelatonin (6-H_aMT). In one set of experiments, the urine samples were subjected to column chromatography to separate the glucuronide and sulfate conjugates for independent analysis. In another, an internal standard (NAS-sulfate) was used for quantification and total conjugate analysis. Measurement was by gas chromatography-mass spectrometry, and the molecular ions of deuterated and nondeuter-ated NAS and 6-H_aMT were monitored. Deuterated _aMT was metabolized to deuterated NAS and deuterated 6-H_aMT. The proportion of NAS was less in the sulfate than in the glucuronide conjugates and, overall, represented 15‰ of the total. Since demethylation is not a pathway that occurs with other pineal methoxyindoles, even at a much larger dose, it seems to be a significant finding with regard to _aMT. Thus, it may be important to elucidate the differential metabolism of _aMT at different time points and in different age groups.