“…In humans, most melatonin in the general circulation is converted to 6-hydroxymelatonin by the liver, which clears 92 to 97% of circulating melatonin in a single pass (Tetsuo et al, 1980;Young et al, 1985). Then 6-hydroxymelatonin FIG. 1.…”
Section: A Melatonin Physiology and Functionmentioning
“…In humans, most melatonin in the general circulation is converted to 6-hydroxymelatonin by the liver, which clears 92 to 97% of circulating melatonin in a single pass (Tetsuo et al, 1980;Young et al, 1985). Then 6-hydroxymelatonin FIG. 1.…”
Section: A Melatonin Physiology and Functionmentioning
“…6-Hydroxyinelatonin is then converted into sulfate and chromatography coupled to mass spectrome try has also been used to measure total conju gated urinary 6-hydroxylated metabolites of melatonin following their hydrolysis [3,5,6]. Radioimmunoassays for urinary [7][8][9][10][11] and plasma [9,11] 6-sulfatoxymelatonin have been developed.…”
A specific, sensitive and reproducible high-performance liquid chromatographic (HPLC) method is described for the simultaneous measurement of 6-hydroxymelatonin and melatonin in rat plasma. Using this technique, a dose-dependent increase in 6-hydroxymelatonin concentration was observed 10 min after administration of different doses of melatonin. Plasma 6-hydroxymelatonin represented 1% of plasma melatonin, irrespective of the melatonin dose administered. After administration of 100 µg melatonin, 6-hydroxymelatonin could be detected in plasma from 7.5 to 60 min. In the same experiment, plasma 6-sulfatoxymelatonin concentrations determined by radioimmunoassay could be detected from 7.5 to 120 min. This HPLC technique allows the measurement of 6-hydroxymelatonin together with melatonin. Combined with an RIA for 6-sulfatoxymelatonin, it could be useful in determining the site of action of drugs affecting melatonin metabolism.
“…This phenolic metabolite, along with its sulphate or glucuronide conjugate, has been detected in rat and human urine by TLC, GC-MS or RIA (3)(4)(5)(6). More recently, a minor metabolite, N-acetyl-5-hydroxytryptamine (III), arising from O-demethylation of melatonin has been identified by GC-MS in rat urine (4,7).…”
Section: Introductionmentioning
confidence: 99%
“…More recently, a minor metabolite, N-acetyl-5-hydroxytryptamine (III), arising from O-demethylation of melatonin has been identified by GC-MS in rat urine (4,7). Metabolites I and II are thought to be the result of hepatic microsomal oxidation although the evidence for this comes principally from in vivo studies (3)(4)(5)(6)(7) where the phenolic metabo- lites or their conjugates have been isolated from rat or human urine. In the present study, the in vitro oxidation of melatonin has been investigated using rat liver microsomes from untreated, phenobarbitone (PB) or benzpyrene (BP) treated animals.…”
Hepatic metabolism of melatonin has been investigated. Melatonin was converted in vitro by rat liver microsomes to 6-hydroxymelatonin and to a lesser extent to N-acetylserotonin. Induction with phenobarbitone caused a fourfold increase in the formation of the minor product with little effect on 6-hydroxymelatonin production or melatonin turnover. In contrast, benzpyrene induction caused a dramatic increase in melatonin turnover but the formation of both metabolites, particularly 6-hydroxymelatonin was significantly reduced. This suggests that an alternative inducible pathway is involved in melatonin catabolism. Chlorpromazine, which elevates plasma melatonin in man and rat, significantly reduced melatonin turnover and reduced the formation of both metabolites in control and phenobarbitone induced microsomes. With benzpyrene induction, chlorpromazine inhibited melatonin turnover but in this group, 6-hydroxymelatonin concentrations were higher than controls. It is thus proposed that the drug preferentially inhibits the alternative benzpyrene inducible isozyme rather than the melatonin hydroxylase.
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