Definition
A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the PINEAL GLAND. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of SLEEP, mood, and REPRODUCTION. Melatonin is also an effective antioxidant. Melatonin, also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants and microbes. In animals, circulating levels of the hormone melatonin vary in a daily cycle, thereby allowing the entrainment of the circadian rhythms of several biological functions. (Wikipedia)
Description
Melatonin is a biogenic amine that is found in animals, plants and microbes. Aaron B. Lerner of Yale University is credited for naming the hormone and for defining its chemical structure in 1958. In mammals, melatonin is produced by the pineal gland. The pineal gland is small endocrine gland, about the size of a rice grain and shaped like a pine cone (hence the name), that is located in the center of the brain (rostro-dorsal to the superior colliculus) but outside the blood-brain barrier. The secretion of melatonin increases in darkness and decreases during exposure to light, thereby regulating the circadian rhythms of several biological functions, including the sleep-wake cycle. In particular, melatonin regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature. Melatonin is also implicated in the regulation of mood, learning and memory, immune activity, dreaming, fertility and reproduction. Melatonin is also an effective antioxidant. Most of the actions of melatonin are mediated through the binding and activation of melatonin receptors. Individuals with autism spectrum disorders (ASD) may have lower than normal levels of melatonin. A 2008 study found that unaffected parents of individuals with ASD also have lower melatonin levels, and that the deficits were associated with low activity of the ASMT gene, which encodes the last enzyme of melatonin synthesis. Reduced melatonin production has also been proposed as a likely factor in the significantly higher cancer rates in night workers.
Top Gene Interactions
Related Pathways
Melatonin Health Effects
- Anaphrodisiac
- Anti convulsant
- Anti depressant
- Anti gonadotrophic
- Anti insomniac
- Antioxidant
- Anti radicular
- Aphrodisiac
- Contraceptive
- Cyclooxygenase-2 inhibitor
- Cyclooxygenase inhibitor
- Depressant
- GABA nergic
- Gonadotrophic
- Hormone
- Hypocholesterolemic
- Hypothermic
- Immunostimulant
- Progesteronigenic
- Serotoninergic
- Thyrotropic
- Anti aggregant
- Anti thyreotropic
- Hypnotic
General Information
- Metabolism:
Hepatically metabolized to at least 14 identified metabolites (identified in mouse urine): 6-hydroxymelatonin glucuronide, 6-hydroxymelatonin sulfate, N-acetylserotonin glucuronide, N-acetylserotonin sulfate, 6-hydroxymelatonin, 2-oxomelatonin, 3-hydroxymelatonin, melatonin glucuronide, cyclic melatonin, cyclic N-acetylserotonin glucuronide, cyclic 6-hydroxymelatonin, 5-hydroxyindole-3-acetaldehyde, di-hydroxymelatonin and its glucuronide conjugate. 6-Hydroxymelatonin glucuronide is the major metabolite found in mouse urine (65-88% of total melatonin metabolites in urine). Half Life: 35 to 50 minutes
- Uses/Sources:
Used orally for jet lag, insomnia, shift-work disorder, circadian rhythm disorders in the blind (evidence for efficacy), and benzodiazepine and nicotine withdrawal. Evidence indicates that melatonin is likely effective for treating circadian rhythm sleep disorders in blind children and adults. It has received FDA orphan drug status as an oral medication for this use. A number of studies have shown that melatonin may be effective for treating sleep-wake cycle disturbances in children and adolescents with mental retardation, autism, and other central nervous system disorders. It appears to decrease the time to fall asleep in children with developmental disabilities, such as cerebral palsy, autism, and mental retardation. It may also improve secondary insomnia associated with various sleep-wake cycle disturbances. Other possible uses for which there is some evidence for include: benzodiazepine withdrawal, cluster headache, delayed sleep phase syndrome (DSPS), primary insomnia, jet lag, nicotine withdrawal, preoperative anxiety and sedation, prostate cancer, solid tumors (when combined with IL-2 therapy in certain cancers), sunburn prevention (topical use), tardive dyskinesia, thrombocytopenia associated with cancer, chemotherapy and other disorders.
- Health Effects: Tolerance can develop, in which the person needs larger doses to achieve the desired effect; this can lead to overdose and death. Accidents or injury can also occur due to the side effects of loss of coordination, slowed reaction time, sleepiness and impaired judgment. Drugs in this category have a high potential for physical and psychological dependence. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
- Symptoms:
Loss of coordination, slowed reaction time, sleepiness and impaired judgment.
- Route of Exposure:
The absorption and bioavailability of melatonin varies widely.
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 3200 mg/kg (Oral, Rat) (A308)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Calmodulin Myeloperoxidase Eosinophil peroxidase 5-hydroxytryptamine receptor 2A 5-hydroxytryptamine receptor 2C 5-hydroxytryptamine receptor 2B Ribosyldihydronicotinamide dehydrogenase [quinone] Nuclear receptor ROR-beta Acetylserotonin O-methyltransferase Melatonin receptor type 1B Calreticulin Metallothionein-3 |
12213063 12646022 15713384 23228808 10737738 21775151 15992934 7961794 15203165 8632342 19449447 21420861 11960497 21568291 14643330 23265885 21377769 9840420 19966183 15380218 23131339 20674373 18237195 18657980 11063602 21392858 12750432 21764185 18400335 20227878 17645693 10455277 19463840 9618428 15013015 15229223 20827520 12643943 9618903 18778943 18372181 17481904 7946354 9435890 12603316 21473625 12061881 16759094 18516076 14980664 7568007 9089668 180879 |
|
Estrogen receptor Alpha-synuclein Melatonin receptor type 1A Apoptosis regulator Bcl-2 Caspase-3 Cytochrome c |
Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate. |
12213063 12646022 15713384 15683469 16635015 23228808 15981996 10737738 21775151 15964511 15203165 21420861 11960497 15796769 21568291 14643330 17286743 23265885 21377769 15380218 20674373 18657980 15750583 11063602 15683462 21392858 21764185 16207299 21726069 20227878 17645693 15800915 17046760 15013015 16421971 16879316 12643943 9804685 18778943 15978052 15854745 18372181 17645694 17481904 16499559 15703542 15978053 17072839 9435890 21473625 12061881 16213988 16759094 16459197 14980664 |