ContaminantDB: Melatonin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (21)XML

Record Information

Version

1.0

Creation Date

2009-07-21 20:28:16 UTC

Update Date

2026-05-14 16:57:10 UTC

Accession Number

CHEM002334

Identification

Common Name

Melatonin

Class

Small Molecule

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.

Contaminant Sources

FooDB Chemicals
HMDB Contaminants - Urine
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Adjuvant, Immunologic
Amide
Amine
Animal Toxin
Anticonvulsant
Antioxidant
Central Nervous System Depressant
Drug
Ether
Food Toxin
Free Radical Scavenger
Metabolite
Natural Compound
Nutraceutical
Organic Compound
Plant Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
5-Methoxy-N-acetyltryptamine	ChEBI
Melatonine	ChEBI
N-[2-(5-Methoxyindol-3-yl)ethyl]acetamide	ChEBI
N-Acetyl-5-methoxytryptamine	ChEBI
Melatonina	Kegg
Circadin	HMDB
Melatol	HMDB
Melatonin (synth.) standard-grade	HMDB
Melatonin (synth.) ultra-pure	HMDB
Melovine	HMDB
MT6	HMDB
N-(2-(5-Methoxy-1H-indol-3-yl)ethyl)acetamide	HMDB
N-(2-(5-Methoxyindol-3-yl)ethyl)-acetamide	HMDB
N-(2-(5-Methoxyindol-3-yl)ethyl)acetamide	HMDB
N-Acetyl-5-methoxy-tryptamine	HMDB
N-Acetyl-5-methoxy-tryptamine melatonine	HMDB
N-[2-(5-Methoxy-1H-indol-3-yl)ethyl)acetamide	HMDB
N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]-acetamide	HMDB
N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide	HMDB
N-[2-(5-Methoxyindol-3-yl)ethyl]-acetamide	HMDB
Regulin	HMDB
{N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-} acetamide	HMDB
{N-[2-(5-methoxyindol-3-yl)ethyl]-} acetamide	HMDB
3-(2-Acetamidoethyl)-5-methoxyindole	HMDB
Melatonin	HMDB

Chemical Formula

C₁₃H₁₆N₂O₂

Average Molecular Mass

232.278 g/mol

Monoisotopic Mass

232.121 g/mol

CAS Registry Number

73-31-4

IUPAC Name

N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide

Traditional Name

melatonin

SMILES

COC1=CC2=C(NC=C2CCNC(C)=O)C=C1

InChI Identifier

InChI=1S/C13H16N2O2/c1-9(16)14-6-5-10-8-15-13-4-3-11(17-2)7-12(10)13/h3-4,7-8,15H,5-6H2,1-2H3,(H,14,16)

InChI Key

DRLFMBDRBRZALE-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as 3-alkylindoles. 3-alkylindoles are compounds containing an indole moiety that carries an alkyl chain at the 3-position.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Indoles and derivatives

Sub Class

Indoles

Direct Parent

3-alkylindoles

Alternative Parents

Substituents

3-alkylindole
Anisole
Alkyl aryl ether
Substituted pyrrole
Benzenoid
Pyrrole
Heteroaromatic compound
Propargyl-type 1,3-dipolar organic compound
Ether
Carboximidic acid derivative
Carboximidic acid
Organic 1,3-dipolar compound
Azacycle
Organic oxygen compound
Hydrocarbon derivative
Organopnictogen compound
Organic nitrogen compound
Organooxygen compound
Organonitrogen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

acetamides (CHEBI:16796 )
tryptamines (CHEBI:16796 )
Indole alkaloids (C01598 )
Melatonin (C01598 )
a small molecule (N-ACETYL-5-METHOXY-TRYPTAMINE )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Adipose Tissue
Adrenal Cortex
Adrenal Gland
Adrenal Medulla
Bladder
Brain
Fibroblasts
Gastrointestinal Tract
Gonads
Gut
Intestine
Kidney
Liver
Nerve Cells
Neuron
Neutrophil
Ovary
Pancreas
Pineal Gland
Placenta
Platelet
Prostate
Skeletal

Pathways

Name	SMPDB Link	KEGG Link
Tryptophan Metabolism	SMP00063	map00380

Applications

Biological Roles

Chemical Roles

radical scavenger

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	117°C
Boiling Point	Not Available
Solubility	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.14 g/L	ALOGPS
logP	1.42	ALOGPS
logP	1.15	ChemAxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	15.8	ChemAxon
pKa (Strongest Basic)	-1.6	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	54.12 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	66.28 m³·mol⁻¹	ChemAxon
Polarizability	25.65 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-001i-0490000000-aa93967315af900a76ce	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-03k9-0900000000-a15ee6def3f8d75b1231	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-001j-0490000000-94ef1be9ab930060778a	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-001i-1490000000-03e24298c7bd1ed4066a	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-001i-1490000000-03e24298c7bd1ed4066a	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-001j-0590000000-63d5e32dd5f7877a4402	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-001i-0590000000-52b3a733f8b49582d3fb	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0229-1900000000-d81c6f617bc486066136	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0076-4920000000-a8d9d614e9f8769a1359	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-00di-0920000000-f90ec9b77e1a245e35a8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-05fr-0900000000-49e4482c65e82ac64b66	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-003r-0900000000-8a4ae0fd610cca992d74	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-0159-0090000000-939a1caf5760c0ba189c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-0006-0930000000-9e6fcea2c634ac9d85a0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-0006-0900000000-ddd29e731a7de56c1808	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-0006-0900000000-34b4fb52810a15ea5bd6	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-001i-0090000000-5ca2df63ec2baefdae8c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-001i-0190000000-5bae6e63e9b40e60e0a4	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-00di-0900000000-529bf6d5c2091993f865	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-00di-0900000000-158a60fe696120b23b41	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-0a5c-0900000000-5e86b2de659ce47762c0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-001i-0900000000-881c0d57239d56c46f2d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	splash10-00di-0910000000-f256f78adbcbeb2464de	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	splash10-0a4i-0900000000-bd15d952a2fc6c5cbb23	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - DI-ESI-qTof , Positive	splash10-05fr-0900000000-7acf9405f4beeb34566c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - DI-ESI-qTof , Positive	splash10-00di-0900000000-13245183cd8c8cd511c3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-05ai-2900000000-07b3d32f002dba733c10	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0159-0090000000-939a1caf5760c0ba189c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0019-0950000000-3561167f9cf6abf87465	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00dr-0900000000-7c590c12649f6abfac96	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-006x-1900000000-6fc07c212072dc15cda1	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-1390000000-afe87f80bc60da102bf6	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0019-3940000000-44812f1a2c7f6216bd23	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052f-9300000000-995e110e7943eff538ad	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-03k9-1900000000-45ee4fdc7acdb33dad3b	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

The absorption and bioavailability of melatonin varies widely.

Mechanism of Toxicity

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. By binding to melatonin receptors 1 and 2, the downstream signallling cascades have various effects in the body. 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 (MT1) and melatonin receptor 2 (MT2). Melatonin and melatonin receptor agonists, on market or in clinical trials, all bind to and activate both receptor types.The binding of the agonists to the receptors has been investigated for over two decades or since 1986. It is somewhat known, but still not fully understood. When melatonin receptor agonists bind to and activate their receptors it causes numerous physiological processes. MT1 receptors are expressed in many regions of the central nervous system (CNS): suprachiasmatic nucleus of the hypothalamus (SNC), hippocampus, substantia nigra, cerebellum, central dopaminergic pathways, ventral tegmental area and nucleus accumbens. MT1 is also expressed in the retina, ovary, testis, mammary gland, coronary circulation and aorta, gallbladder, liver, kidney, skin and the immune system. MT2 receptors are expressed mainly in the CNS, also in the lung, cardiac, coronary and aortic tissue, myometrium and granulosa cells, immune cells, duodenum and adipocytes. The binding of melatonin to melatonin receptors activates a few signaling pathways. MT1 receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activation; starting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorilation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT1 receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell. The binding of melatonin to MT2 receptors inhibits adenylyl cyclase which decreases the formation of cAMP.[4] As well it hinders guanylyl cyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT2 receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell.

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

Toxicity Values

LD50: 3200 mg/kg (Oral, Rat) (1)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

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.

Minimum Risk Level

Not Available

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.

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

DB01065

HMDB ID

HMDB0001389

FooDB ID

FDB004234

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

37965

BioCyc ID

N-ACETYL-5-METHOXY-TRYPTAMINE

METLIN ID

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

Not Available

ECMDB ID

M2MDB005304

References

Synthesis Reference

Robert A. S. Welch, Keith Betteridge, “Method of stimulating cashmere growth on cashmere-producing goats using melatonin.” U.S. Patent US4855313, issued August, 1986.

MSDS

Link

General References

1. Eriksson L, Valtonen M, Laitinen JT, Paananen M, Kaikkonen M: Diurnal rhythm of melatonin in bovine milk: pharmacokinetics of exogenous melatonin in lactating cows and goats. Acta Vet Scand. 1998;39(3):301-10.

2. Helmut M. Hügel and Faizul Nurlawis. Short synthesis of melatonin. Heterocycles (2003), Vol. 60, No. 10, pp. 2349 - 2354.

3. Drake MJ, Mills IW, Noble JG: Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement. J Urol. 2004 Mar;171(3):1199-202.

4. Slominski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J: Functional activity of serotoninergic and melatoninergic systems expressed in the skin. J Cell Physiol. 2003 Jul;196(1):144-53.

5. Lahiri DK, Chen D, Lahiri P, Rogers JT, Greig NH, Bondy S: Melatonin, metals, and gene expression: implications in aging and neurodegenerative disorders. Ann N Y Acad Sci. 2004 Dec;1035:216-30.

6. Bangha E, Lauth D, Kistler GS, Elsner P: Daytime serum levels of melatonin after topical application onto the human skin. Skin Pharmacol. 1997;10(5-6):298-302.

7. Bubenik GA: Localization, physiological significance and possible clinical implication of gastrointestinal melatonin. Biol Signals Recept. 2001 Nov-Dec;10(6):350-66.

8. Christofides J, Bridel M, Egerton M, Mackay GM, Forrest CM, Stoy N, Darlington LG, Stone TW: Blood 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and melatonin levels in patients with either Huntington's disease or chronic brain injury. J Neurochem. 2006 May;97(4):1078-88. Epub 2006 Mar 29.

9. Abdel-Wahhab MA, Abdel-Galil MM, El-Lithey M: Melatonin counteracts oxidative stress in rats fed an ochratoxin A contaminated diet. J Pineal Res. 2005 Mar;38(2):130-5.