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 |
17645693 21473625 15992934 21392858 7961794 23131339 12643943 12061881 9618428 19449447 19966183 15713384 12750432 18400335 23228808 7946354 18372181 9089668 14980664 16759094 10455277 18237195 11063602 19463840 21775151 15013015 23265885 7568007 21377769 21568291 15203165 18657980 10737738 9618903 20827520 12646022 15380218 20674373 17481904 12603316 180879 9435890 12213063 21420861 11960497 18516076 20227878 15229223 14643330 9840420 8632342 21764185 18778943 |
|
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. |
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