6Hydroxymelatonin

6-Hydroxymelatonin, sometimes abbreviated 6-OHM, is a hydroxylated metabolite of the pineal hormone melatonin. It is formed in humans primarily by hydroxylation at the 6-position of the indole ring, a reaction catalyzed by cytochrome P450 enzymes. Among these, CYP1A2 is a major contributor, with other isoforms such as CYP1A1 and CYP2C19 likely participating to lesser extents. Formation occurs mainly in the liver but can take place in other tissues exposed to melatonin.

After its formation, 6-hydroxymelatonin is rapidly conjugated with sulfate to form 6-sulfatoxymelatonin, which is excreted in urine. Measurement of urinary 6-sulfatoxymelatonin is widely used as a noninvasive biomarker of endogenous melatonin production and circadian rhythm, reflecting nocturnal melatonin secretion. Plasma levels of 6-hydroxymelatonin can be detected briefly after melatonin administration but are less commonly used clinically due to rapid metabolism.

Biological significance is less well defined than that of melatonin. The activity of 6-hydroxymelatonin itself is not as well characterized, and it is generally regarded more as a metabolite contributing to melatonin pharmacokinetics and disposition than as an active signaling molecule. Research on 6-OHM has aided understanding of melatonin metabolism and its analytical measurement in biological fluids.