In vivo formation of 5-methoxytryptamine from melatonin in rat.

Deacetylation of melatonin to 5-methoxytryptamine (5-MT) in vitro and in vivo was investigated in rat liver and brain tissue, using a gas chromatographic--mass spectrometric 5-MT assay method. In vitro incubation of liver but not brain (hypothalamic, Mesencephalic) slices with melatonin led to a concentration-dependent formation of small amounts of 5-MT; the conversion being 0.3--0.8%. In vivo administration of melatonin resulted in a dose-dependent formation of 5-MT in small quantities in the liver. The time course showed a peak maximum within 0.5 h, with a rapid decline; the half-life being about 1 h. 5-MT could be detected in both the blood and the hypothalamus after in vivo injection of melatonin. The time course of 5-MT in the blood was similar to that in the liver, but 5-MT could only be detected in the hypothalamus after large doses shortly after the melatonin injection. MAO had to be inhibited both in the in vitro and in vivo experiments in order to recover 5-MT, indicating that formed 5-MT is normally rapidly metabolised by MAO. It is concluded that a small fraction of melatonin can be converted to 5-MT by deacetylation (by aryl acylamidase) in the liver in vivo, constituting a minor pathway. Such a pathway could not be demonstrated in the brain. Trace amounts of 5-MT previously reported to be present in various tissues could originate from deacetylation of melatonin in the liver and possibly some other peripheral organs known to contain the deacetylating enzyme. The present results indicate that peripherally formed 5-MT, a psychoactive compound, is unlikely to have any effect on brain function under normal circumstances.