Physiology and available preparations of melatonin
- Richard Wurtman, MD
Richard Wurtman, MD
- Cecil H Green Distinguished Professor
- Department of Brain and Cognitive Sciences
- Massachusetts Institute of Technology
Melatonin is a hormone produced in the pineal gland from the amino acid tryptophan and secreted into the blood and cerebrospinal fluid. It conveys signals to distant organs, principally the brain, and affects the synthesis of second messengers and, ultimately, sleep and circadian rhythms.
The physiology of melatonin and an overview of its clinical uses are reviewed here. Additional information on clinical uses of melatonin are found separately. (See "Treatment of insomnia in adults", section on 'Melatonin agonists' and "Jet lag" and "Complementary and alternative therapies for cancer", section on 'Melatonin'.)
The human pineal gland is an important structure that transmits signals to the brain and other organs by secreting its unique hormone, melatonin. However this concept is only a few decades old. In 1975, it was discovered that melatonin production in humans, like that in all other mammals studied, exhibits a pronounced circadian rhythm such that nocturnal plasma melatonin concentrations are at least 10-fold higher than daytime concentrations [1,2]. In humans, nocturnal serum concentrations of melatonin decline across puberty , but no reproductive effects of exogenous melatonin have been clearly demonstrated .
Much pineal research has concerned the human brain's responses to melatonin rhythms. The most compelling evidence supports two roles for melatonin in humans: the involvement of nocturnal melatonin secretion in initiating and maintaining sleep, and control by the day/night melatonin rhythm of the timing of other 24-hour rhythms. Melatonin's effect on sleep underlies most of its current use as a drug and the development of melatonin analogs as new drugs [5,6]. (See 'Circadian rhythm' below and 'Melatonin agonists' below.)
Synthesis and metabolism — Almost all of the melatonin formed in mammals is synthesized within the pineal gland from the essential amino acid tryptophan (figure 1) . Plasma melatonin and its circadian rhythm largely or completely disappear among pinealectomized animals  or human subjects post-pinealectomy . Tryptophan is first 5-hydroxylated by the enzyme tryptophan hydroxylase and then decarboxylated by the enzyme aromatic L-amino acid decarboxylase to form 5-hydroxytryptamine, or serotonin (figure 1) .
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- MELATONIN PHYSIOLOGY
- Synthesis and metabolism
- Circadian rhythm
- Plasma concentrations
- - Age
- - Effects of drugs or light
- - Patients with nocturnal hypertension
- MELATONIN PREPARATIONS
- Regulatory issues
- - Dosing
- - Bioavailability
- - Prolonged-release formulation
- Melatonin agonists
- Adverse effects
- CLINICAL USES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS