General
Preferred name
MELATONIN
Synonyms
N-(2-(5-methoxy-1h-indol-3-yl)ethyl)acetamide ()
N-Acetyl-5-methoxytryptamine ()
Melatonine ()
melatonin, Alliance ()
Melatonin (NSC 113928) ()
NSC 56423, N-Acetyl-5-methoxytryptamine,NSC 113928,MT ()
Melatol ()
Melovine ()
Icenia ()
Melapure ()
Quality Health ()
Tartrol ()
Life Ext ()
General Nutrit ()
NSC-56423 ()
Nature's Blend ()
NSC-302012 ()
Natrol ()
NSC-113928 ()
Travelag ()
Natures Bounty ()
Regulin ()
BCI-049 ()
5-methoxy n-acetyl-tryptamine ()
N-(2-(5-Methoxy-1H-Indol-3-Yl)Ethyl)Acetamide ()
S.Gard ()
Circadin ()
J5.258B ()
Vespro ()
Vytalonin ()
Heidadouppi ()
Health Aid ()
Melatonin-d4 ()
P&D ID
PD001629
CAS
73-31-4
51023-76-8
66521-38-8
Tags
natural product
drug
available
Approved by
PMDA
EMA
FDA
First approval
2007
Drug Status
nutraceutical
approved
vet_approved
Drug indication
Insomnia
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS 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 by light. High levels of melatonin induce sleep and so consumption of the drug can be used to combat insomnia and jet lag.; MT1 and MT2 receptors may be a target for the treatment of circadian and non circadian sleep disorders because of their differences in pharmacology and function within the SCN. SCN is responsible for maintaining the 24 hour cycle which regulates many different body functions ranging from sleep to immune functions;
DESCRIPTION Melatonin is a hormone involved in regulating circadian rhythms in animals. Melatonin activates a family of melatonin receptors.

SARS-CoV-2 and COVID-19: The effect of viral infection (including by influenza and SARS-CoV-2) on the melatonergic pathway, and how this might modulate the inflammatory response was reviewed by Anderson and Reiter in May 2020 . (GtoPdb)
MOA 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.
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, 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

;
DESCRIPTION Potent NPY Y5 receptor antagonist (Tocris Bioactive Compound Library)
DESCRIPTION Endogenous hormone; agonist at MT1 and MT2 (Tocriscreen Plus)
DESCRIPTION Endogenous neurohormone which controls photo-periodic biological rhythms (LOPAC library)
DESCRIPTION Endogenous hormone; agonist at MT1 and MT2 (Tocriscreen Total)
Cell lines
3
Organisms
1
Compound Sets
35
AdooQ Bioactive Compound Library
A10564
Cayman Chemical Bioactives
14427
22291
ChEMBL Approved Drugs
CHEMBL45
ChEMBL Drugs
CHEMBL45
Concise Guide to Pharmacology 2017/18
1357
224
Concise Guide to Pharmacology 2019/20
1357
224
Concise Guide to Pharmacology 2021/22
1357
224
Concise Guide to Pharmacology 2023/24
1357
224
Drug Repurposing Hub
DrugBank
DB01065
DrugBank Approved Drugs
DB01065
DrugCentral
1672
DrugCentral Approved Drugs
1672
DrugMAP
DMKWFBT
DrugMAP Approved Drugs
DMKWFBT
DrugMatrix
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS100717
Guide to Pharmacology
1357
224
Ki Database
MELATONIN
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL45
MedChem Express Bioactive Compound Library
HY-B0075
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
NURSA ligand set
nursa/index.jsf?doi=10.1621%2F8DVWM6W3LN
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Melatonin
TargetMol Bioactive Compound Library
T1659
The Spectrum Collection
Tocris Bioactive Compound Library
3550
Tocriscreen Plus
3550
Tocriscreen Total
ZINC Tool Compounds
ZINC000000057060
External IDs
49
Properties
(calculated by RDKit )
Molecular Weight
232.12
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
2
Rotatable Bonds
4
Ring Count
2
Aromatic Ring Count
2
cLogP
1.86
TPSA
54.12
Fraction CSP3
0.31
Chiral centers
0.0
Largest ring
6.0
QED
0.84
QED
0.84
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Pathway
Endocrinology/Hormones
GPCR/G protein
Metabolism
Neuroscience
Apoptosis
Autophagy
Metabolic Enzyme/Protease
Neuronal Signaling
Target
CAM
ER
Melatonin Receptor
MPO
ROR??
ASMT, CALM1, CALR, EPX, ESR1, HTR2B, MPO, MTNR1A, MTNR1B, NQO2, RORB
Endogenous Metabolite
Mitophagy
Apoptosis related,ATF/CREB & c-Fos/c-Jun,Autophagy,COX,Mitophagy,MT Receptor
Primary Target
Melatonin Receptors
MOA
Agonist
Antioxidants
Apoptosis Inducers
Free radical scavengers
NOS2 Expression Inhibitors
TH Expression Enhancers
melatonin receptor agonist, nitric oxide synthase inhibitor
Member status
virtual
Indication
sleep cycle support
Therapeutic Class
Central Nervous System Stimulants
Source data