Description

Simple

A naturally occurring hormone that promotes sleep.

Clinical

An endogenous hormone produced by the pineal gland that regulates sleep-wake cycles and when provided exogenously has beneficial effects on sleep-onset latency; available as an over-the-counter supplement.

Overview

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... Read more

Pharmacology

Indication

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 ha... Read more

Pharmacodynamic

Melatonin is a hormone normally produced in the pineal gland and released into the blood. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. It helps regulate sleep-wake cycles or the circadian rhythm. Production of melatonin is stimulated by darkness and inhibited b... Read more

Mechanism of action

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 arachid... Read more

Absorption

The absorption and bioavailability of melatonin varies widely.

Protein binding

n/a

Volume of distribution

Information currently not available.

Clearance

Information currently not available.

Half life

35 to 50 minutes

Route of elimination

Information currently not available.

Toxicity

Generally well-tolerated when taken orally. The most common side effects, day-time drowsiness, headache and dizziness, appear to occur at the same frequency as with placebo. Other reported side effects include transient depressive symptoms, mild tremor, mild anxiety, abdominal cramps, irritabilit... Read more

Generally well-tolerated when taken orally. The most common side effects, day-time drowsiness, headache and dizziness, appear to occur at the same frequency as with placebo. Other reported side effects include transient depressive symptoms, mild tremor, mild anxiety, abdominal cramps, irritability, reduced alertness, confusion, nausea, vomiting, and hypotension. Safety in Adults: Evidence indicates that it is likely safe to use in oral and parenteral forms for up to two months when used appropriately. Some evidence indicates that it can be safely used orally for up to 9 months in some patients. It is also likely safe to use topically when used appropriately. Safety in Children: Melatonin appeared to be used safely in small numbers of children enrolled in short-term clinical trials. However, concerns regarding safety in children have arisen based on their developmental state. Compared to adults over 20 years of age, people under 20 produce high levels of melatonin. Melatonin levels are inversely related to gonadal development and it is thought that exogenous administration of melatonin may adversely affect gonadal development. Safety during Pregnancy: High doses of melatonin administered orally or parenterally may inhibit ovulation. Not advised for use in individuals who are pregnant or trying to become pregnant. Safety during Lactation: Not recommended as safety has not be established.


Oral, rat: LD50 ≥3200 mg/kg


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Adverse Effects

Contraindications

Information currently not available.

Food Interactions

    Information currently not available.

Interactions

Type in a drug name to check for interaction with Melatonin
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be decreased when combined with Melatonin.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Melatonin.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when Melatonin is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when Melatonin is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Melatonin is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Melatonin is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanine
The metabolism of 6-O-benzylguanine can be decreased when combined with Melatonin.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Melatonin is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of adverse effects can be increased when Melatonin is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
8-azaguanine
The metabolism of 8-azaguanine can be decreased when combined with Melatonin.
8-chlorotheophylline
The metabolism of 8-chlorotheophylline can be decreased when combined with Melatonin.
9-Deazaguanine
The metabolism of 9-Deazaguanine can be decreased when combined with Melatonin.
9-Methylguanine
The metabolism of 9-Methylguanine can be decreased when combined with Melatonin.
Abatacept
The metabolism of Melatonin can be increased when combined with Abatacept.
Abiraterone
The serum concentration of Melatonin can be increased when it is combined with Abiraterone.
Acefylline
The metabolism of Acefylline can be decreased when combined with Melatonin.
Acenocoumarol
The metabolism of Acenocoumarol can be decreased when combined with Melatonin.
Acepromazine
The risk or severity of adverse effects can be increased when Melatonin is combined with Acepromazine.
Aceprometazine
The risk or severity of adverse effects can be increased when Melatonin is combined with Aceprometazine.
Acetaminophen
The metabolism of Melatonin can be decreased when combined with Acetaminophen.
6 References
  1. 1 . Boutin JA, Audinot V, Ferry G, Delagrange P: Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci. 2005 Aug;26(8):412-9.PubMed: 15992934
  2. 2 . Caniato R, Filippini R, Piovan A, Puricelli L, Borsarini A, Cappelletti EM: Melatonin in plants. Adv Exp Med Biol. 2003;527:593-7.PubMed: 15206778
  3. 3 . Hardeland R: Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2005 Jul;27(2):119-30.PubMed: 16217125
  4. 4 . Hattori A, Migitaka H, Iigo M, Itoh M, Yamamoto K, Ohtani-Kaneko R, Hara M, Suzuki T, Reiter RJ: Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates. Biochem Mol Biol Int. 1995 Mar;35(3):627-34.PubMed: 7773197
  5. 5 . Ma X, Chen C, Krausz KW, Idle JR, Gonzalez FJ: A metabolomic perspective of melatonin metabolism in the mouse. Endocrinology. 2008 Apr;149(4):1869-79. doi: 10.1210/en.2007-1412. Epub 2008 Jan 10.PubMed: 18187545
  6. 6 . Reiter RJ, Acuna-Castroviejo D, Tan DX, Burkhardt S: Free radical-mediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system. Ann N Y Acad Sci. 2001 Jun;939:200-15.PubMed: 11462772