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In humans, 90% of orally administered exogenous melatonin is cleared in a single passage through the liver, a small amount is excreted in urine, and a small amount is found in saliva. [13] Melatonin is excreted in the urine 2 to 5% as the unchanged drug. [6] [8] Melatonin has an elimination half-life of about 20 to 60 minutes.
Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. [1] Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cows that could induce skin lightening in common frogs.
The melatonin receptors are G protein-coupled receptors and are expressed in various tissues of the body. There are two subtypes of the receptor in humans, melatonin receptor 1 (MT 1) and melatonin receptor 2 (MT 2). [2] Melatonin and melatonin receptor agonists, on market or in clinical trials, all bind to and activate both receptor types. [1]
Melatonin receptors are G protein-coupled receptors (GPCR) which bind melatonin. [1] Three types of melatonin receptors have been cloned.The MT 1 (or Mel 1A or MTNR1A) and MT 2 (or Mel 1B or MTNR1B) receptor subtypes are present in humans and other mammals, [2] while an additional melatonin receptor subtype MT 3 (or Mel 1C or MTNR1C) has been identified in amphibia and birds. [3]
Melatonin is an endogenous hormone synthesized in the pineal gland in the brain involved in promoting sleep. [30] It activates both melatonin receptors MT1 and MT2 to produce beneficial effects on sleep, therefore being used exogenously for mild insomnia. [ 31 ]
TIK-301 (LY-156735) is an agonist for the melatonin receptors MT 1 and MT 2 that is under development for the treatment of insomnia and other sleep disorders. [1] Its agonist action on MT 1 and MT 2 receptors in the suprachiasmatic nucleus in the brain enables its action as a chronobiotic.
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