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Identification
NameMelatonin
Accession NumberDB01065  (APRD00742, DB08189)
TypeSmall Molecule
GroupsApproved, Nutraceutical, Vet Approved
DescriptionMelatonin 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.
Structure
Thumb
Synonyms
5-methoxy-N-acetyltryptamine
Melatonin
Melatonine
N-[2-(5-methoxyindol-3-yl)ethyl]acetamide
N-Acetyl-5-methoxytryptamine
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CircadinTablet, extended release2 mgOralRad Neurim Pharmaceuticals Eec Limited2007-06-29Not applicableEu
CircadinTablet, extended release2 mgOralRad Neurim Pharmaceuticals Eec Limited2007-06-29Not applicableEu
CircadinTablet, extended release2 mgOralRad Neurim Pharmaceuticals Eec Limited2007-06-29Not applicableEu
CircadinTablet, extended release2 mgOralRad Neurim Pharmaceuticals Eec Limited2007-06-29Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CircadinLundbeck (France, United Kingdom), Neurim Pharmaceutical Labs (Israel, Denmark, Greece, Norway, Poland, Portugal), Nycomed (Belgium, Sweden)
Mela-TAlacer Corp. (Canada)
MelatolElisium (Argentina)
MelatoninBiomed International Products Corp., Nutravite Pharmaceuticals (2008) Inc., Viva Pharmaceutical Inc., Kripps Pharmacy Ltd., SunOpta Inc.
Nature'S HarmonySunOpta Inc. (Canada)
Revital MelatoninChin Tai Ginseng Co., Ltd (Canada)
Rx BalanceSunOpta Inc. (Canada)
Sleep RightSunOpta Inc. (Canada)
VivitasSunOpta Inc. (Canada)
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIJL5DK93RCL
CAS number73-31-4
WeightAverage: 232.2783
Monoisotopic: 232.121177766
Chemical FormulaC13H16N2O2
InChI KeyDRLFMBDRBRZALE-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide
SMILES
COC1=CC2=C(NC=C2CCNC(C)=O)C=C1
Pharmacology
IndicationUsed 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.
Structured Indications Not Available
PharmacodynamicsMelatonin 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
Mechanism of actionMelatonin 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Melatonin receptor type 1AProteinyes
agonist
HumanP48039 details
Melatonin receptor type 1BProteinyes
agonist
HumanP49286 details
Estrogen receptorProteinunknown
antagonist
HumanP03372 details
Nuclear receptor ROR-betaProteinunknown
agonist
HumanQ92753 details
CalmodulinProteinunknownNot AvailableHumanP62158 details
MyeloperoxidaseProteinunknown
inhibitor
HumanP05164 details
Eosinophil peroxidaseProteinunknown
inhibitor
HumanP11678 details
CalreticulinProteinunknownNot AvailableHumanP27797 details
Acetylserotonin O-methyltransferaseProteinunknownNot AvailableHumanP46597 details
Ribosyldihydronicotinamide dehydrogenase [quinone]ProteinunknownNot AvailableHumanP16083 details
Related Articles
AbsorptionThe absorption and bioavailability of melatonin varies widely.
Volume of distributionNot Available
Protein bindingn/a
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).

SubstrateEnzymesProduct
Melatonin
6-HydroxymelatoninDetails
Melatonin
N-Acetyl-5-hydroxytryptamineDetails
6-Hydroxymelatonin
Not Available
6-Hydroxymelatonin sulfateDetails
N-Acetyl-5-hydroxytryptamine
Not Available
N-Acetyl-5-hydroxytryptamine sulfateDetails
N-Acetyl-5-hydroxytryptamine
N-Acetyl-5-hydroxytryptamine glucuronideDetails
6-Hydroxymelatonin
6-Hydroxymelatonin glucuronideDetails
Melatonin
Not Available
5-MethoxytryptamineDetails
5-Methoxytryptamine
Not Available
PinolineDetails
5-Methoxytryptamine
Not Available
BufotenineDetails
Bufotenine
Not Available
N,N-DimethyltryptamineDetails
Route of eliminationNot Available
Half life35 to 50 minutes
ClearanceNot 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, 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

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Tryptophan MetabolismMetabolicSMP00063
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
1,1,1,2 TetrafluoroethaneThe risk or severity of adverse effects can be increased when Melatonin is combined with 1,1,1,2 Tetrafluoroethane.Investigational
7-NitroindazoleThe risk or severity of adverse effects can be increased when Melatonin is combined with 7-Nitroindazole.Experimental
AbirateroneThe serum concentration of Melatonin can be increased when it is combined with Abiraterone.Approved
AcepromazineThe risk or severity of adverse effects can be increased when Melatonin is combined with Acepromazine.Approved, Vet Approved
AceprometazineThe risk or severity of adverse effects can be increased when Melatonin is combined with Aceprometazine.Approved
adipiplonThe risk or severity of adverse effects can be increased when Melatonin is combined with adipiplon.Investigational
AgomelatineThe risk or severity of adverse effects can be increased when Melatonin is combined with Agomelatine.Approved, Investigational
AlfaxaloneThe risk or severity of adverse effects can be increased when Melatonin is combined with Alfaxalone.Vet Approved
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Melatonin.Approved, Illicit
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Melatonin is combined with Alphacetylmethadol.Experimental, Illicit
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Melatonin.Approved, Illicit, Investigational
AmiodaroneThe metabolism of Melatonin can be decreased when combined with Amiodarone.Approved, Investigational
AmisulprideThe risk or severity of adverse effects can be increased when Melatonin is combined with Amisulpride.Approved, Investigational
AmitriptylineThe risk or severity of adverse effects can be increased when Melatonin is combined with Amitriptyline.Approved
AmlodipineMelatonin may decrease the antihypertensive activities of Amlodipine.Approved
AmobarbitalThe risk or severity of adverse effects can be increased when Melatonin is combined with Amobarbital.Approved, Illicit
AmoxapineThe risk or severity of adverse effects can be increased when Melatonin is combined with Amoxapine.Approved
AmperozideThe risk or severity of adverse effects can be increased when Melatonin is combined with Amperozide.Experimental
AprepitantThe metabolism of Melatonin can be increased when combined with Aprepitant.Approved, Investigational
AripiprazoleThe risk or severity of adverse effects can be increased when Melatonin is combined with Aripiprazole.Approved, Investigational
ArmodafinilThe metabolism of Melatonin can be decreased when combined with Armodafinil.Approved, Investigational
ArticaineThe risk or severity of adverse effects can be increased when Melatonin is combined with Articaine.Approved
AsenapineThe risk or severity of adverse effects can be increased when Melatonin is combined with Asenapine.Approved
AzaperoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Azaperone.Vet Approved
AzelastineMelatonin may increase the central nervous system depressant (CNS depressant) activities of Azelastine.Approved
AzelastineThe risk or severity of adverse effects can be increased when Melatonin is combined with Azelastine.Approved
AzithromycinThe metabolism of Melatonin can be decreased when combined with Azithromycin.Approved
BaclofenThe risk or severity of adverse effects can be increased when Melatonin is combined with Baclofen.Approved
BarbitalThe risk or severity of adverse effects can be increased when Melatonin is combined with Barbital.Illicit
BenperidolThe risk or severity of adverse effects can be increased when Melatonin is combined with Benperidol.Investigational
BenzocaineThe risk or severity of adverse effects can be increased when Melatonin is combined with Benzocaine.Approved
Benzyl alcoholThe risk or severity of adverse effects can be increased when Melatonin is combined with Benzyl alcohol.Approved
BortezomibThe metabolism of Melatonin can be decreased when combined with Bortezomib.Approved, Investigational
BrexpiprazoleThe risk or severity of adverse effects can be increased when Melatonin is combined with Brexpiprazole.Approved
BrimonidineThe risk or severity of adverse effects can be increased when Melatonin is combined with Brimonidine.Approved
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved
BromazepamThe risk or severity of adverse effects can be increased when Melatonin is combined with Bromazepam.Approved, Illicit
BrompheniramineThe risk or severity of adverse effects can be increased when Melatonin is combined with Brompheniramine.Approved
BrotizolamThe risk or severity of adverse effects can be increased when Melatonin is combined with Brotizolam.Approved, Withdrawn
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Melatonin.Approved, Investigational
BuprenorphineMelatonin may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Melatonin.Approved, Investigational
ButabarbitalThe risk or severity of adverse effects can be increased when Butabarbital is combined with Melatonin.Approved, Illicit
ButacaineThe risk or severity of adverse effects can be increased when Melatonin is combined with Butacaine.Vet Approved
ButalbitalThe risk or severity of adverse effects can be increased when Melatonin is combined with Butalbital.Approved, Illicit
ButambenThe risk or severity of adverse effects can be increased when Melatonin is combined with Butamben.Approved
ButethalThe risk or severity of adverse effects can be increased when Melatonin is combined with Butethal.Approved, Illicit
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Melatonin.Approved, Illicit, Vet Approved
CaffeineThe metabolism of Melatonin can be decreased when combined with Caffeine.Approved
CapecitabineThe metabolism of Melatonin can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Melatonin can be increased when combined with Carbamazepine.Approved, Investigational
CarbinoxamineThe risk or severity of adverse effects can be increased when Melatonin is combined with Carbinoxamine.Approved
CarfentanilThe risk or severity of adverse effects can be increased when Melatonin is combined with Carfentanil.Illicit, Vet Approved
CarisoprodolThe risk or severity of adverse effects can be increased when Melatonin is combined with Carisoprodol.Approved
CeritinibThe serum concentration of Melatonin can be increased when it is combined with Ceritinib.Approved
CetirizineThe risk or severity of adverse effects can be increased when Melatonin is combined with Cetirizine.Approved
Chloral hydrateThe risk or severity of adverse effects can be increased when Melatonin is combined with Chloral hydrate.Approved, Illicit, Vet Approved
ChloramphenicolThe metabolism of Melatonin can be decreased when combined with Chloramphenicol.Approved, Vet Approved
ChlordiazepoxideThe risk or severity of adverse effects can be increased when Chlordiazepoxide is combined with Melatonin.Approved, Illicit
ChlormezanoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Chlormezanone.Approved, Withdrawn
ChloroprocaineThe risk or severity of adverse effects can be increased when Melatonin is combined with Chloroprocaine.Approved
ChlorphenamineThe risk or severity of adverse effects can be increased when Melatonin is combined with Chlorphenamine.Approved
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Melatonin.Approved, Vet Approved
ChlorprothixeneThe risk or severity of adverse effects can be increased when Melatonin is combined with Chlorprothixene.Approved, Withdrawn
ChlorzoxazoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Chlorzoxazone.Approved
CholecalciferolThe metabolism of Melatonin can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Melatonin can be decreased when combined with Cimetidine.Approved
CinchocaineThe risk or severity of adverse effects can be increased when Cinchocaine is combined with Melatonin.Approved, Vet Approved
CitalopramThe metabolism of Melatonin can be decreased when combined with Citalopram.Approved
ClemastineThe risk or severity of adverse effects can be increased when Melatonin is combined with Clemastine.Approved
ClevidipineMelatonin may decrease the antihypertensive activities of Clevidipine.Approved
ClidiniumThe risk or severity of adverse effects can be increased when Melatonin is combined with Clidinium.Approved
ClobazamThe risk or severity of adverse effects can be increased when Melatonin is combined with Clobazam.Approved, Illicit
clomethiazoleThe risk or severity of adverse effects can be increased when Melatonin is combined with clomethiazole.Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Melatonin is combined with Clomipramine.Approved, Vet Approved
ClonazepamThe risk or severity of adverse effects can be increased when Melatonin is combined with Clonazepam.Approved, Illicit
ClonidineThe risk or severity of adverse effects can be increased when Melatonin is combined with Clonidine.Approved
ClorazepateThe risk or severity of adverse effects can be increased when Clorazepate is combined with Melatonin.Approved, Illicit
ClotrimazoleThe metabolism of Melatonin can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Melatonin.Approved
CocaineThe risk or severity of adverse effects can be increased when Cocaine is combined with Melatonin.Approved, Illicit
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Melatonin.Approved, Illicit
CyclizineThe risk or severity of adverse effects can be increased when Melatonin is combined with Cyclizine.Approved
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Melatonin.Approved
CyclosporineThe metabolism of Melatonin can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CyproheptadineThe risk or severity of adverse effects can be increased when Melatonin is combined with Cyproheptadine.Approved
Cyproterone acetateThe serum concentration of Melatonin can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Melatonin can be decreased when it is combined with Dabrafenib.Approved
DantroleneThe risk or severity of adverse effects can be increased when Melatonin is combined with Dantrolene.Approved
DapiprazoleThe risk or severity of adverse effects can be increased when Dapiprazole is combined with Melatonin.Approved
DapoxetineThe risk or severity of adverse effects can be increased when Melatonin is combined with Dapoxetine.Investigational
DeferasiroxThe serum concentration of Melatonin can be increased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Melatonin can be decreased when combined with Delavirdine.Approved
deramciclaneThe risk or severity of adverse effects can be increased when Melatonin is combined with deramciclane.Investigational
DesfluraneThe risk or severity of adverse effects can be increased when Melatonin is combined with Desflurane.Approved
DesipramineThe risk or severity of adverse effects can be increased when Melatonin is combined with Desipramine.Approved
DesloratadineThe risk or severity of adverse effects can be increased when Melatonin is combined with Desloratadine.Approved, Investigational
DesvenlafaxineThe risk or severity of adverse effects can be increased when Melatonin is combined with Desvenlafaxine.Approved
DetomidineThe risk or severity of adverse effects can be increased when Melatonin is combined with Detomidine.Vet Approved
DexbrompheniramineThe risk or severity of adverse effects can be increased when Melatonin is combined with Dexbrompheniramine.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Melatonin.Approved, Vet Approved
DextromoramideThe risk or severity of adverse effects can be increased when Melatonin is combined with Dextromoramide.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Melatonin.Approved, Illicit, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Melatonin is combined with Dezocine.Approved
DiazepamThe risk or severity of adverse effects can be increased when Diazepam is combined with Melatonin.Approved, Illicit, Vet Approved
DifenoxinThe risk or severity of adverse effects can be increased when Melatonin is combined with Difenoxin.Approved, Illicit
DihydrocodeineThe risk or severity of adverse effects can be increased when Melatonin is combined with Dihydrocodeine.Approved, Illicit
DihydroetorphineThe risk or severity of adverse effects can be increased when Melatonin is combined with Dihydroetorphine.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Melatonin is combined with Dihydromorphine.Experimental, Illicit
DimenhydrinateThe risk or severity of adverse effects can be increased when Melatonin is combined with Dimenhydrinate.Approved
DiphenhydramineThe risk or severity of adverse effects can be increased when Melatonin is combined with Diphenhydramine.Approved
DiphenoxylateThe risk or severity of adverse effects can be increased when Melatonin is combined with Diphenoxylate.Approved, Illicit
DoramectinThe risk or severity of adverse effects can be increased when Melatonin is combined with Doramectin.Vet Approved
DoxepinThe risk or severity of adverse effects can be increased when Melatonin is combined with Doxepin.Approved
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved, Vet Approved
DPDPEThe risk or severity of adverse effects can be increased when Melatonin is combined with DPDPE.Investigational
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved, Illicit
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved, Vet Approved
DrotebanolThe risk or severity of adverse effects can be increased when Melatonin is combined with Drotebanol.Experimental, Illicit
DuloxetineThe risk or severity of adverse effects can be increased when Melatonin is combined with Duloxetine.Approved
DyclonineThe risk or severity of adverse effects can be increased when Dyclonine is combined with Melatonin.Approved
EcgonineThe risk or severity of adverse effects can be increased when Melatonin is combined with Ecgonine.Experimental, Illicit
ECGONINE METHYL ESTERThe risk or severity of adverse effects can be increased when Melatonin is combined with ECGONINE METHYL ESTER.Experimental
EcopipamThe risk or severity of adverse effects can be increased when Melatonin is combined with Ecopipam.Investigational
EfavirenzThe risk or severity of adverse effects can be increased when Melatonin is combined with Efavirenz.Approved, Investigational
EnfluraneThe risk or severity of adverse effects can be increased when Enflurane is combined with Melatonin.Approved, Vet Approved
EntacaponeThe risk or severity of adverse effects can be increased when Melatonin is combined with Entacapone.Approved, Investigational
EscitalopramThe risk or severity of adverse effects can be increased when Melatonin is combined with Escitalopram.Approved, Investigational
Eslicarbazepine acetateThe metabolism of Melatonin can be decreased when combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Melatonin can be decreased when combined with Esomeprazole.Approved, Investigational
EstazolamThe risk or severity of adverse effects can be increased when Melatonin is combined with Estazolam.Approved, Illicit
EszopicloneThe risk or severity of adverse effects can be increased when Eszopiclone is combined with Melatonin.Approved
EthanolMelatonin may increase the central nervous system depressant (CNS depressant) activities of Ethanol.Approved
EthchlorvynolThe risk or severity of adverse effects can be increased when Ethchlorvynol is combined with Melatonin.Approved, Illicit, Withdrawn
EthosuximideThe risk or severity of adverse effects can be increased when Melatonin is combined with Ethosuximide.Approved
EthotoinThe risk or severity of adverse effects can be increased when Melatonin is combined with Ethotoin.Approved
Ethyl carbamateThe risk or severity of adverse effects can be increased when Melatonin is combined with Ethyl carbamate.Withdrawn
Ethyl loflazepateThe risk or severity of adverse effects can be increased when Melatonin is combined with Ethyl loflazepate.Approved, Illicit
EthylmorphineThe risk or severity of adverse effects can be increased when Melatonin is combined with Ethylmorphine.Approved, Illicit
EtidocaineThe risk or severity of adverse effects can be increased when Melatonin is combined with Etidocaine.Approved
EtifoxineThe risk or severity of adverse effects can be increased when Melatonin is combined with Etifoxine.Withdrawn
EtizolamThe risk or severity of adverse effects can be increased when Melatonin is combined with Etizolam.Approved
EtomidateThe risk or severity of adverse effects can be increased when Etomidate is combined with Melatonin.Approved
EtoperidoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Etoperidone.Approved
EtorphineThe risk or severity of adverse effects can be increased when Melatonin is combined with Etorphine.Illicit, Vet Approved
EtravirineThe metabolism of Melatonin can be decreased when combined with Etravirine.Approved
EzogabineThe risk or severity of adverse effects can be increased when Melatonin is combined with Ezogabine.Approved
FelbamateThe risk or severity of adverse effects can be increased when Melatonin is combined with Felbamate.Approved
FelodipineMelatonin may decrease the antihypertensive activities of Felodipine.Approved, Investigational
FencamfamineThe risk or severity of adverse effects can be increased when Melatonin is combined with Fencamfamine.Approved, Illicit, Withdrawn
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Melatonin.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe risk or severity of adverse effects can be increased when Melatonin is combined with Fexofenadine.Approved
FlibanserinThe risk or severity of adverse effects can be increased when Melatonin is combined with Flibanserin.Approved
FloxuridineThe metabolism of Melatonin can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Melatonin can be decreased when combined with Fluconazole.Approved
FludiazepamThe risk or severity of adverse effects can be increased when Melatonin is combined with Fludiazepam.Approved, Illicit
FlunarizineThe risk or severity of adverse effects can be increased when Melatonin is combined with Flunarizine.Approved
FlunitrazepamThe risk or severity of adverse effects can be increased when Melatonin is combined with Flunitrazepam.Approved, Illicit
FluorouracilThe metabolism of Melatonin can be decreased when combined with Fluorouracil.Approved
FluoxetineThe metabolism of Melatonin can be decreased when combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe risk or severity of adverse effects can be increased when Flupentixol is combined with Melatonin.Approved, Withdrawn
FluphenazineThe risk or severity of adverse effects can be increased when Fluphenazine is combined with Melatonin.Approved
FlurazepamThe risk or severity of adverse effects can be increased when Flurazepam is combined with Melatonin.Approved, Illicit
FluspirileneThe risk or severity of adverse effects can be increased when Melatonin is combined with Fluspirilene.Approved
Fluticasone PropionateThe risk or severity of adverse effects can be increased when Melatonin is combined with Fluticasone Propionate.Approved
FluvastatinThe metabolism of Melatonin can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Melatonin can be decreased when combined with Fluvoxamine.Approved, Investigational
FosphenytoinThe metabolism of Melatonin can be increased when combined with Fosphenytoin.Approved
FospropofolThe risk or severity of adverse effects can be increased when Melatonin is combined with Fospropofol.Approved, Illicit
GabapentinThe risk or severity of adverse effects can be increased when Gabapentin is combined with Melatonin.Approved, Investigational
gabapentin enacarbilThe risk or severity of adverse effects can be increased when Melatonin is combined with gabapentin enacarbil.Approved
Gamma Hydroxybutyric AcidThe risk or severity of adverse effects can be increased when Melatonin is combined with Gamma Hydroxybutyric Acid.Approved, Illicit
GemfibrozilThe metabolism of Melatonin can be decreased when combined with Gemfibrozil.Approved
GepironeThe risk or severity of adverse effects can be increased when Melatonin is combined with Gepirone.Investigational
GlutethimideThe risk or severity of adverse effects can be increased when Melatonin is combined with Glutethimide.Approved, Illicit
GuanfacineThe risk or severity of adverse effects can be increased when Melatonin is combined with Guanfacine.Approved, Investigational
HalazepamThe risk or severity of adverse effects can be increased when Halazepam is combined with Melatonin.Approved, Illicit, Withdrawn
HaloperidolThe risk or severity of adverse effects can be increased when Haloperidol is combined with Melatonin.Approved
HalothaneThe risk or severity of adverse effects can be increased when Melatonin is combined with Halothane.Approved, Vet Approved
HeroinThe risk or severity of adverse effects can be increased when Melatonin is combined with Heroin.Approved, Illicit
HexobarbitalThe risk or severity of adverse effects can be increased when Melatonin is combined with Hexobarbital.Approved
HydrocodoneMelatonin may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.Approved, Illicit
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Melatonin.Approved, Illicit
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved
IloperidoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Iloperidone.Approved
ImipramineThe risk or severity of adverse effects can be increased when Melatonin is combined with Imipramine.Approved
IndalpineThe risk or severity of adverse effects can be increased when Melatonin is combined with Indalpine.Investigational, Withdrawn
IndinavirThe metabolism of Melatonin can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Melatonin can be decreased when combined with Irbesartan.Approved, Investigational
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Melatonin.Approved, Vet Approved
IsoniazidThe metabolism of Melatonin can be decreased when combined with Isoniazid.Approved
IsradipineMelatonin may decrease the antihypertensive activities of Isradipine.Approved
KetamineThe risk or severity of adverse effects can be increased when Melatonin is combined with Ketamine.Approved, Vet Approved
KetazolamThe risk or severity of adverse effects can be increased when Melatonin is combined with Ketazolam.Approved
KetobemidoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Ketobemidone.Approved
KetoconazoleThe metabolism of Melatonin can be decreased when combined with Ketoconazole.Approved, Investigational
LamotrigineThe risk or severity of adverse effects can be increased when Melatonin is combined with Lamotrigine.Approved, Investigational
LeflunomideThe metabolism of Melatonin can be decreased when combined with Leflunomide.Approved, Investigational
LevetiracetamThe risk or severity of adverse effects can be increased when Melatonin is combined with Levetiracetam.Approved, Investigational
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Melatonin.Approved
LevocabastineThe risk or severity of adverse effects can be increased when Melatonin is combined with Levocabastine.Approved
LevocetirizineThe risk or severity of adverse effects can be increased when Melatonin is combined with Levocetirizine.Approved
LevodopaThe risk or severity of adverse effects can be increased when Melatonin is combined with Levodopa.Approved
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Melatonin is combined with Levomethadyl Acetate.Approved
LevomilnacipranThe risk or severity of adverse effects can be increased when Melatonin is combined with Levomilnacipran.Approved
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Melatonin.Approved
LidocaineThe metabolism of Melatonin can be decreased when combined with Lidocaine.Approved, Vet Approved
LithiumThe risk or severity of adverse effects can be increased when Melatonin is combined with Lithium.Approved
LofentanilThe risk or severity of adverse effects can be increased when Melatonin is combined with Lofentanil.Illicit
LopinavirThe metabolism of Melatonin can be increased when combined with Lopinavir.Approved
LoratadineThe risk or severity of adverse effects can be increased when Melatonin is combined with Loratadine.Approved
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Melatonin.Approved
LosartanThe metabolism of Melatonin can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Melatonin can be decreased when combined with Lovastatin.Approved, Investigational
LoxapineThe risk or severity of adverse effects can be increased when Loxapine is combined with Melatonin.Approved
Lu AA21004The risk or severity of adverse effects can be increased when Melatonin is combined with Lu AA21004.Investigational
LuliconazoleThe serum concentration of Melatonin can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Melatonin can be decreased when it is combined with Lumacaftor.Approved
LurasidoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Lurasidone.Approved
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved, Vet Approved
MaprotilineThe risk or severity of adverse effects can be increased when Melatonin is combined with Maprotiline.Approved
MeclizineThe risk or severity of adverse effects can be increased when Melatonin is combined with Meclizine.Approved
MedetomidineThe risk or severity of adverse effects can be increased when Melatonin is combined with Medetomidine.Vet Approved
MelperoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Melperone.Approved
MepivacaineThe risk or severity of adverse effects can be increased when Mepivacaine is combined with Melatonin.Approved, Vet Approved
MeprobamateThe risk or severity of adverse effects can be increased when Meprobamate is combined with Melatonin.Approved, Illicit
MesoridazineThe risk or severity of adverse effects can be increased when Mesoridazine is combined with Melatonin.Approved
MetaxaloneThe risk or severity of adverse effects can be increased when Melatonin is combined with Metaxalone.Approved
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Melatonin.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Melatonin is combined with Methadyl Acetate.Approved, Illicit
MethapyrileneThe risk or severity of adverse effects can be increased when Melatonin is combined with Methapyrilene.Withdrawn
MethaqualoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Methaqualone.Illicit, Withdrawn
MethocarbamolThe risk or severity of adverse effects can be increased when Melatonin is combined with Methocarbamol.Approved, Vet Approved
MethohexitalThe risk or severity of adverse effects can be increased when Methohexital is combined with Melatonin.Approved
MethotrimeprazineMelatonin may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.Approved
MethoxyfluraneThe risk or severity of adverse effects can be increased when Methoxyflurane is combined with Melatonin.Approved, Vet Approved
MethsuximideThe risk or severity of adverse effects can be increased when Melatonin is combined with Methsuximide.Approved
MethylphenobarbitalThe risk or severity of adverse effects can be increased when Methylphenobarbital is combined with Melatonin.Approved
MetyrosineMelatonin may increase the sedative activities of Metyrosine.Approved
MexiletineThe metabolism of Melatonin can be decreased when combined with Mexiletine.Approved
MidazolamThe risk or severity of adverse effects can be increased when Midazolam is combined with Melatonin.Approved, Illicit
MifepristoneThe serum concentration of Melatonin can be increased when it is combined with Mifepristone.Approved, Investigational
MilnacipranThe risk or severity of adverse effects can be increased when Melatonin is combined with Milnacipran.Approved
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved, Investigational
MirtazapineMelatonin may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.Approved
MoclobemideThe metabolism of Melatonin can be decreased when combined with Moclobemide.Approved
ModafinilThe metabolism of Melatonin can be decreased when combined with Modafinil.Approved, Investigational
MolindoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Molindone.Approved
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Melatonin.Approved, Investigational
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved, Investigational
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Melatonin.Approved
NefazodoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Melatonin can be decreased when combined with Nelfinavir.Approved
NevirapineThe metabolism of Melatonin can be decreased when combined with Nevirapine.Approved
NicardipineMelatonin may decrease the antihypertensive activities of Nicardipine.Approved
NifedipineMelatonin may decrease the antihypertensive activities of Nifedipine.Approved
NimodipineMelatonin may decrease the antihypertensive activities of Nimodipine.Approved
NisoldipineMelatonin may decrease the antihypertensive activities of Nisoldipine.Approved
NitrazepamThe risk or severity of adverse effects can be increased when Melatonin is combined with Nitrazepam.Approved
Nitrous oxideThe risk or severity of adverse effects can be increased when Melatonin is combined with Nitrous oxide.Approved, Vet Approved
NormethadoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Normethadone.Approved, Illicit
NortriptylineThe risk or severity of adverse effects can be increased when Melatonin is combined with Nortriptyline.Approved
OlanzapineThe risk or severity of adverse effects can be increased when Olanzapine is combined with Melatonin.Approved, Investigational
OlopatadineThe risk or severity of adverse effects can be increased when Melatonin is combined with Olopatadine.Approved
OmeprazoleThe metabolism of Melatonin can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OndansetronThe risk or severity of adverse effects can be increased when Ondansetron is combined with Melatonin.Approved
OpiumThe risk or severity of adverse effects can be increased when Melatonin is combined with Opium.Approved, Illicit
OrphenadrineMelatonin may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.Approved
OsanetantThe risk or severity of adverse effects can be increased when Melatonin is combined with Osanetant.Investigational
OsimertinibThe serum concentration of Melatonin can be decreased when it is combined with Osimertinib.Approved
OxazepamThe risk or severity of adverse effects can be increased when Oxazepam is combined with Melatonin.Approved
OxetacaineThe risk or severity of adverse effects can be increased when Melatonin is combined with Oxetacaine.Investigational
OxprenololThe risk or severity of adverse effects can be increased when Melatonin is combined with Oxprenolol.Approved
OxybuprocaineThe risk or severity of adverse effects can be increased when Oxybuprocaine is combined with Melatonin.Approved
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Melatonin.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Oxymorphone.Approved, Investigational, Vet Approved
PaliperidoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Paliperidone.Approved
PantoprazoleThe metabolism of Melatonin can be decreased when combined with Pantoprazole.Approved
ParaldehydeMelatonin may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.Approved
ParoxetineThe risk or severity of adverse effects can be increased when Melatonin is combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Melatonin can be increased when it is combined with Peginterferon alfa-2b.Approved
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Melatonin.Approved, Vet Approved
PentobarbitalThe risk or severity of adverse effects can be increased when Pentobarbital is combined with Melatonin.Approved, Vet Approved
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved
PerazineThe risk or severity of adverse effects can be increased when Melatonin is combined with Perazine.Investigational
PerospironeThe risk or severity of adverse effects can be increased when Melatonin is combined with Perospirone.Approved
PerphenazineThe risk or severity of adverse effects can be increased when Perphenazine is combined with Melatonin.Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Melatonin.Approved
PhenobarbitalThe metabolism of Melatonin can be increased when combined with Phenobarbital.Approved
PhenoxyethanolThe risk or severity of adverse effects can be increased when Melatonin is combined with Phenoxyethanol.Approved
PhenytoinThe metabolism of Melatonin can be increased when combined with Phenytoin.Approved, Vet Approved
PimozideThe risk or severity of adverse effects can be increased when Melatonin is combined with Pimozide.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Melatonin is combined with Pipamperone.Approved
PipotiazineThe risk or severity of adverse effects can be increased when Melatonin is combined with Pipotiazine.Approved
PiritramideThe risk or severity of adverse effects can be increased when Melatonin is combined with Piritramide.Investigational
PizotifenThe risk or severity of adverse effects can be increased when Melatonin is combined with Pizotifen.Approved
PomalidomideThe risk or severity of adverse effects can be increased when Melatonin is combined with Pomalidomide.Approved
PramipexoleMelatonin may increase the sedative activities of Pramipexole.Approved, Investigational
PramocaineThe risk or severity of adverse effects can be increased when Melatonin is combined with Pramocaine.Approved
PrazepamThe risk or severity of adverse effects can be increased when Melatonin is combined with Prazepam.Approved, Illicit
PregabalinThe risk or severity of adverse effects can be increased when Pregabalin is combined with Melatonin.Approved, Illicit, Investigational
PregnanoloneThe risk or severity of adverse effects can be increased when Melatonin is combined with Pregnanolone.Investigational
PrilocaineThe risk or severity of adverse effects can be increased when Prilocaine is combined with Melatonin.Approved
PrimidoneThe metabolism of Melatonin can be increased when combined with Primidone.Approved, Vet Approved
ProcaineThe risk or severity of adverse effects can be increased when Procaine is combined with Melatonin.Approved, Investigational, Vet Approved
ProchlorperazineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with Melatonin.Approved, Vet Approved
PromazineThe risk or severity of adverse effects can be increased when Promazine is combined with Melatonin.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Melatonin is combined with Promethazine.Approved
ProparacaineThe risk or severity of adverse effects can be increased when Proparacaine is combined with Melatonin.Approved, Vet Approved
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Melatonin.Approved, Investigational, Vet Approved
PropoxycaineThe risk or severity of adverse effects can be increased when Melatonin is combined with Propoxycaine.Approved
ProtriptylineThe risk or severity of adverse effects can be increased when Melatonin is combined with Protriptyline.Approved
PSD502The risk or severity of adverse effects can be increased when Melatonin is combined with PSD502.Investigational
PyrimethamineThe metabolism of Melatonin can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuazepamThe risk or severity of adverse effects can be increased when Melatonin is combined with Quazepam.Approved, Illicit
QuetiapineThe risk or severity of adverse effects can be increased when Melatonin is combined with Quetiapine.Approved
QuinineThe metabolism of Melatonin can be decreased when combined with Quinine.Approved
RacloprideThe risk or severity of adverse effects can be increased when Melatonin is combined with Raclopride.Investigational
RamelteonThe risk or severity of adverse effects can be increased when Melatonin is combined with Ramelteon.Approved, Investigational
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Melatonin.Approved
RemoxiprideThe risk or severity of adverse effects can be increased when Remoxipride is combined with Melatonin.Approved, Withdrawn
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Melatonin.Approved
RifampicinThe metabolism of Melatonin can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Melatonin can be increased when combined with Rifapentine.Approved
RisperidoneThe risk or severity of adverse effects can be increased when Risperidone is combined with Melatonin.Approved, Investigational
RitanserinThe risk or severity of adverse effects can be increased when Melatonin is combined with Ritanserin.Investigational
RomifidineThe risk or severity of adverse effects can be increased when Melatonin is combined with Romifidine.Vet Approved
RopiniroleMelatonin may increase the sedative activities of Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Ropivacaine is combined with Melatonin.Approved
RotigotineMelatonin may increase the sedative activities of Rotigotine.Approved
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Melatonin.Approved
S-EthylisothioureaThe risk or severity of adverse effects can be increased when Melatonin is combined with S-Ethylisothiourea.Experimental
Sage 547The risk or severity of adverse effects can be increased when Melatonin is combined with Sage 547.Investigational
ScopolamineThe risk or severity of adverse effects can be increased when Melatonin is combined with Scopolamine.Approved
SecobarbitalThe metabolism of Melatonin can be increased when combined with Secobarbital.Approved, Vet Approved
SertindoleThe risk or severity of adverse effects can be increased when Melatonin is combined with Sertindole.Approved, Withdrawn
SertralineThe metabolism of Melatonin can be decreased when combined with Sertraline.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Melatonin is combined with Sevoflurane.Approved, Vet Approved
SildenafilThe metabolism of Melatonin can be decreased when combined with Sildenafil.Approved, Investigational
SimeprevirThe metabolism of Melatonin can be decreased when combined with Simeprevir.Approved
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved
SorafenibThe metabolism of Melatonin can be decreased when combined with Sorafenib.Approved, Investigational
StiripentolThe metabolism of Melatonin can be decreased when combined with Stiripentol.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Melatonin.Approved, Investigational
SulfadiazineThe metabolism of Melatonin can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Melatonin can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Melatonin can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SulpirideThe risk or severity of adverse effects can be increased when Sulpiride is combined with Melatonin.Approved
SuvorexantMelatonin may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.Approved
TandospironeThe risk or severity of adverse effects can be increased when Melatonin is combined with Tandospirone.Investigational
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Melatonin.Approved
TasimelteonThe risk or severity of adverse effects can be increased when Melatonin is combined with Tasimelteon.Approved
TemazepamThe risk or severity of adverse effects can be increased when Temazepam is combined with Melatonin.Approved
TenofovirThe metabolism of Melatonin can be decreased when combined with Tenofovir.Approved, Investigational
TeriflunomideThe serum concentration of Melatonin can be decreased when it is combined with Teriflunomide.Approved
TetrabenazineThe risk or severity of adverse effects can be increased when Melatonin is combined with Tetrabenazine.Approved
TetracaineThe risk or severity of adverse effects can be increased when Melatonin is combined with Tetracaine.Approved, Vet Approved
TetrodotoxinThe risk or severity of adverse effects can be increased when Melatonin is combined with Tetrodotoxin.Investigational
ThalidomideMelatonin may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.Approved, Investigational, Withdrawn
TheophyllineThe metabolism of Melatonin can be decreased when combined with Theophylline.Approved
ThiamylalThe risk or severity of adverse effects can be increased when Melatonin is combined with Thiamylal.Approved, Vet Approved
ThiopentalThe risk or severity of adverse effects can be increased when Thiopental is combined with Melatonin.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Thioridazine is combined with Melatonin.Approved
ThiothixeneThe risk or severity of adverse effects can be increased when Melatonin is combined with Thiothixene.Approved
TiagabineThe risk or severity of adverse effects can be increased when Melatonin is combined with Tiagabine.Approved
TiaprideThe risk or severity of adverse effects can be increased when Melatonin is combined with Tiapride.Investigational
TicagrelorThe metabolism of Melatonin can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Melatonin can be decreased when combined with Ticlopidine.Approved
TiletamineThe risk or severity of adverse effects can be increased when Melatonin is combined with Tiletamine.Vet Approved
TizanidineThe risk or severity of adverse effects can be increased when Melatonin is combined with Tizanidine.Approved
TolbutamideThe metabolism of Melatonin can be decreased when combined with Tolbutamide.Approved
TolcaponeThe risk or severity of adverse effects can be increased when Melatonin is combined with Tolcapone.Approved, Withdrawn
TopiramateThe risk or severity of adverse effects can be increased when Melatonin is combined with Topiramate.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Melatonin.Approved, Investigational
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Melatonin is combined with Trans-2-Phenylcyclopropylamine.Experimental
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Melatonin.Approved
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Melatonin.Approved, Investigational
TriazolamThe risk or severity of adverse effects can be increased when Triazolam is combined with Melatonin.Approved
TrifluoperazineThe risk or severity of adverse effects can be increased when Trifluoperazine is combined with Melatonin.Approved
TriflupromazineThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Melatonin.Approved, Vet Approved
TrimethoprimThe metabolism of Melatonin can be decreased when combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe risk or severity of adverse effects can be increased when Melatonin is combined with Trimipramine.Approved
TriprolidineThe risk or severity of adverse effects can be increased when Melatonin is combined with Triprolidine.Approved
Uc1010The risk or severity of adverse effects can be increased when Melatonin is combined with Uc1010.Investigational
Valproic AcidThe risk or severity of adverse effects can be increased when Valproic Acid is combined with Melatonin.Approved, Investigational
ValsartanThe metabolism of Melatonin can be decreased when combined with Valsartan.Approved, Investigational
VemurafenibThe serum concentration of Melatonin can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe risk or severity of adverse effects can be increased when Melatonin is combined with Venlafaxine.Approved
VigabatrinThe risk or severity of adverse effects can be increased when Melatonin is combined with Vigabatrin.Approved
VoriconazoleThe metabolism of Melatonin can be decreased when combined with Voriconazole.Approved, Investigational
VortioxetineThe risk or severity of adverse effects can be increased when Melatonin is combined with Vortioxetine.Approved
XylazineThe risk or severity of adverse effects can be increased when Melatonin is combined with Xylazine.Vet Approved
ZafirlukastThe metabolism of Melatonin can be decreased when combined with Zafirlukast.Approved, Investigational
ZaleplonThe risk or severity of adverse effects can be increased when Zaleplon is combined with Melatonin.Approved, Illicit, Investigational
ZiconotideThe risk or severity of adverse effects can be increased when Melatonin is combined with Ziconotide.Approved
ZimelidineThe risk or severity of adverse effects can be increased when Melatonin is combined with Zimelidine.Withdrawn
ZiprasidoneThe risk or severity of adverse effects can be increased when Ziprasidone is combined with Melatonin.Approved
ZolazepamThe risk or severity of adverse effects can be increased when Melatonin is combined with Zolazepam.Vet Approved
ZolpidemMelatonin may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.Approved
ZonisamideThe risk or severity of adverse effects can be increased when Melatonin is combined with Zonisamide.Approved, Investigational
ZopicloneThe risk or severity of adverse effects can be increased when Melatonin is combined with Zopiclone.Approved
ZotepineThe risk or severity of adverse effects can be increased when Melatonin is combined with Zotepine.Approved
ZuclopenthixolThe risk or severity of adverse effects can be increased when Melatonin is combined with Zuclopenthixol.Approved, Investigational
Food InteractionsNot Available
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.

US4855313
General References
  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. 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. 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. 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. 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. 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 ]
External Links
ATC CodesN05CH01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (72 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9928
Caco-2 permeable-0.5536
P-glycoprotein substrateSubstrate0.6188
P-glycoprotein inhibitor INon-inhibitor0.9569
P-glycoprotein inhibitor IINon-inhibitor0.6838
Renal organic cation transporterNon-inhibitor0.542
CYP450 2C9 substrateNon-substrate0.8231
CYP450 2D6 substrateSubstrate0.5062
CYP450 3A4 substrateSubstrate0.6505
CYP450 1A2 substrateInhibitor0.9304
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8084
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.7194
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6803
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9498
BiodegradationNot ready biodegradable0.8764
Rat acute toxicity1.8922 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9631
hERG inhibition (predictor II)Non-inhibitor0.5124
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tablet, extended releaseOral2 mg
Prices
Unit descriptionCostUnit
Melatonin powder45.6USD g
Melatonin 3 mg tablet0.22USD tablet
Melatonin 5 mg tablet0.12USD tablet
Melatonin 5 mg tablet sl0.1USD tablet
Melatonin sublingual tablet0.09USD tablet
Melatonin 1 mg tablet0.03USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point117 °CPhysProp
logP1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.143 mg/mLALOGPS
logP1.42ALOGPS
logP1.15ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)15.8ChemAxon
pKa (Strongest Basic)-0.94ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area54.12 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity66.28 m3·mol-1ChemAxon
Polarizability25.65 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.2 KB)
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-001i-0490000000-aa93967315af900a76ceView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-03k9-0900000000-a15ee6def3f8d75b1231View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-001j-0490000000-94ef1be9ab930060778aView in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-001i-1490000000-03e24298c7bd1ed4066aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00di-0920000000-f90ec9b77e1a245e35a8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-05fr-0900000000-49e4482c65e82ac64b66View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-003r-0900000000-8a4ae0fd610cca992d74View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-0159-0090000000-939a1caf5760c0ba189cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0006-0930000000-9e6fcea2c634ac9d85a0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0006-0900000000-ddd29e731a7de56c1808View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0006-0900000000-34b4fb52810a15ea5bd6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-001i-0090000000-5ca2df63ec2baefdae8cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-001i-0190000000-5bae6e63e9b40e60e0a4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-00di-0900000000-529bf6d5c2091993f865View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-00di-0900000000-158a60fe696120b23b41View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-0a5c-0900000000-5e86b2de659ce47762c0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-001i-0900000000-881c0d57239d56c46f2dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-00di-0910000000-f256f78adbcbeb2464deView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-0a4i-0900000000-bd15d952a2fc6c5cbb23View in MoNA
MSMass Spectrum (Electron Ionization)splash10-03k9-1900000000-45ee4fdc7acdb33dad3bView in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as serotonins. These are compounds containing a serotonin moiety, which consists of an indole that bears an aminoethyl a position 2 and a hydroxyl group at position 5.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassTryptamines and derivatives
Direct ParentSerotonins
Alternative Parents
Substituents
  • Serotonin
  • Hydroxyindole
  • Indole
  • Anisole
  • Alkyl aryl ether
  • Benzenoid
  • Substituted pyrrole
  • Heteroaromatic compound
  • Acetamide
  • Pyrrole
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Ether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Organic cyclic compound binding
Specific Function:
High affinity receptor for melatonin. Likely to mediates the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.
Gene Name:
MTNR1A
Uniprot ID:
P48039
Molecular Weight:
39374.315 Da
References
  1. Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. doi: 10.1016/j.taap.2009.05.012. Epub 2009 May 19. [PubMed:19463840 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  3. 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 ]
  4. Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. doi: 10.1002/biof.23. [PubMed:19449447 ]
  5. Srinivasan V, Singh J, Pandi-Perumal SR, Brown GM, Spence DW, Cardinali DP: Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs. Adv Ther. 2010 Nov;27(11):796-813. doi: 10.1007/s12325-010-0065-y. Epub 2010 Sep 6. [PubMed:20827520 ]
  6. Carocci A, Catalano A, Lovece A, Lentini G, Duranti A, Lucini V, Pannacci M, Scaglione F, Franchini C: Design, synthesis, and pharmacological effects of structurally simple ligands for MT(1) and MT(2) melatonin receptors. Bioorg Med Chem. 2010 Sep 1;18(17):6496-511. doi: 10.1016/j.bmc.2010.06.100. Epub 2010 Jul 3. [PubMed:20674373 ]
  7. Prendergast BJ: MT1 melatonin receptors mediate somatic, behavioral, and reproductive neuroendocrine responses to photoperiod and melatonin in Siberian hamsters (Phodopus sungorus). Endocrinology. 2010 Feb;151(2):714-21. doi: 10.1210/en.2009-0710. Epub 2009 Dec 4. [PubMed:19966183 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Melatonin receptor activity
Specific Function:
High affinity receptor for melatonin. Likely to mediates the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.
Gene Name:
MTNR1B
Uniprot ID:
P49286
Molecular Weight:
40187.895 Da
References
  1. Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. doi: 10.1016/j.taap.2009.05.012. Epub 2009 May 19. [PubMed:19463840 ]
  2. 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 ]
  3. Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. doi: 10.1002/biof.23. [PubMed:19449447 ]
  4. Srinivasan V, Singh J, Pandi-Perumal SR, Brown GM, Spence DW, Cardinali DP: Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs. Adv Ther. 2010 Nov;27(11):796-813. doi: 10.1007/s12325-010-0065-y. Epub 2010 Sep 6. [PubMed:20827520 ]
  5. Carocci A, Catalano A, Lovece A, Lentini G, Duranti A, Lucini V, Pannacci M, Scaglione F, Franchini C: Design, synthesis, and pharmacological effects of structurally simple ligands for MT(1) and MT(2) melatonin receptors. Bioorg Med Chem. 2010 Sep 1;18(17):6496-511. doi: 10.1016/j.bmc.2010.06.100. Epub 2010 Jul 3. [PubMed:20674373 ]
  6. Prendergast BJ: MT1 melatonin receptors mediate somatic, behavioral, and reproductive neuroendocrine responses to photoperiod and melatonin in Siberian hamsters (Phodopus sungorus). Endocrinology. 2010 Feb;151(2):714-21. doi: 10.1210/en.2009-0710. Epub 2009 Dec 4. [PubMed:19966183 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription fact...
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
References
  1. del Rio B, Garcia Pedrero JM, Martinez-Campa C, Zuazua P, Lazo PS, Ramos S: Melatonin, an endogenous-specific inhibitor of estrogen receptor alpha via calmodulin. J Biol Chem. 2004 Sep 10;279(37):38294-302. Epub 2004 Jun 30. [PubMed:15229223 ]
  2. Yoo YM, Jeung EB: Melatonin-induced estrogen receptor alpha-mediated calbindin-D9k expression plays a role in H2O2-mediated cell death in rat pituitary GH3 cells. J Pineal Res. 2009 Nov;47(4):301-7. doi: 10.1111/j.1600-079X.2009.00714.x. Epub 2009 Oct 1. [PubMed:19796047 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for nor...
Gene Name:
RORB
Uniprot ID:
Q92753
Molecular Weight:
53219.385 Da
References
  1. Becker-Andre M, Wiesenberg I, Schaeren-Wiemers N, Andre E, Missbach M, Saurat JH, Carlberg C: Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily. J Biol Chem. 1994 Nov 18;269(46):28531-4. [PubMed:7961794 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Titin binding
Specific Function:
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis.
Gene Name:
CALM1
Uniprot ID:
P62158
Molecular Weight:
16837.47 Da
References
  1. del Rio B, Garcia Pedrero JM, Martinez-Campa C, Zuazua P, Lazo PS, Ramos S: Melatonin, an endogenous-specific inhibitor of estrogen receptor alpha via calmodulin. J Biol Chem. 2004 Sep 10;279(37):38294-302. Epub 2004 Jun 30. [PubMed:15229223 ]
  2. Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. doi: 10.1016/j.taap.2009.05.012. Epub 2009 May 19. [PubMed:19463840 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Peroxidase activity
Specific Function:
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.
Gene Name:
MPO
Uniprot ID:
P05164
Molecular Weight:
83867.71 Da
References
  1. Galijasevic S, Abdulhamid I, Abu-Soud HM: Melatonin is a potent inhibitor for myeloperoxidase. Biochemistry. 2008 Feb 26;47(8):2668-77. doi: 10.1021/bi702016q. Epub 2008 Feb 1. [PubMed:18237195 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Peroxidase activity
Specific Function:
Mediates tyrosine nitration of secondary granule proteins in mature resting eosinophils. Shows significant inhibitory activity towards Mycobacterium tuberculosis H37Rv by inducing bacterial fragmentation and lysis.
Gene Name:
EPX
Uniprot ID:
P11678
Molecular Weight:
81039.5 Da
References
  1. Lu T, Galijasevic S, Abdulhamid I, Abu-Soud HM: Analysis of the mechanism by which melatonin inhibits human eosinophil peroxidase. Br J Pharmacol. 2008 Jul;154(6):1308-17. doi: 10.1038/bjp.2008.173. Epub 2008 Jun 2. [PubMed:18516076 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Zinc ion binding
Specific Function:
Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export. Involved in maternal gene expression ...
Gene Name:
CALR
Uniprot ID:
P27797
Molecular Weight:
48141.2 Da
References
  1. Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. doi: 10.1002/biof.23. [PubMed:19449447 ]
  2. Macias M, Escames G, Leon J, Coto A, Sbihi Y, Osuna A, Acuna-Castroviejo D: Calreticulin-melatonin. An unexpected relationship. Eur J Biochem. 2003 Mar;270(5):832-40. [PubMed:12603316 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein homodimerization activity
Specific Function:
Isoform 1 catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine). Isoform 2 and isoform 3 lack enzyme activity.
Gene Name:
ASMT
Uniprot ID:
P46597
Molecular Weight:
38452.51 Da
References
  1. Minneman KP, Wurtman RJ: The pharmacology of the pineal gland. Annu Rev Pharmacol Toxicol. 1976;16:33-51. [PubMed:180879 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Nadph dehydrogenase (quinone) activity
Specific Function:
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
Gene Name:
NQO2
Uniprot ID:
P16083
Molecular Weight:
25918.4 Da
References
  1. Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. doi: 10.1016/j.taap.2009.05.012. Epub 2009 May 19. [PubMed:19463840 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d 24-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
References
  1. Chang TK, Chen J, Yang G, Yeung EY: Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin. J Pineal Res. 2010 Jan;48(1):55-64. doi: 10.1111/j.1600-079X.2009.00724.x. Epub 2009 Nov 16. [PubMed:19919601 ]
  2. Ma X, Idle JR, Krausz KW, Gonzalez FJ: Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005 Apr;33(4):489-94. Epub 2004 Dec 22. [PubMed:15616152 ]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Chang TK, Chen J, Yang G, Yeung EY: Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin. J Pineal Res. 2010 Jan;48(1):55-64. doi: 10.1111/j.1600-079X.2009.00724.x. Epub 2009 Nov 16. [PubMed:19919601 ]
  2. Ma X, Idle JR, Krausz KW, Gonzalez FJ: Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005 Apr;33(4):489-94. Epub 2004 Dec 22. [PubMed:15616152 ]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  4. Turpeinen M, Uusitalo J, Jalonen J, Pelkonen O: Multiple P450 substrates in a single run: rapid and comprehensive in vitro interaction assay. Eur J Pharm Sci. 2005 Jan;24(1):123-32. [PubMed:15626586 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compou...
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular Weight:
60845.33 Da
References
  1. Chang TK, Chen J, Yang G, Yeung EY: Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin. J Pineal Res. 2010 Jan;48(1):55-64. doi: 10.1111/j.1600-079X.2009.00724.x. Epub 2009 Nov 16. [PubMed:19919601 ]
  2. Ma X, Idle JR, Krausz KW, Gonzalez FJ: Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005 Apr;33(4):489-94. Epub 2004 Dec 22. [PubMed:15616152 ]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Huuhka K, Riutta A, Haataja R, Ylitalo P, Leinonen E: The effect of CYP2C19 substrate on the metabolism of melatonin in the elderly: A randomized, double-blind, placebo-controlled study. Methods Find Exp Clin Pharmacol. 2006 Sep;28(7):447-50. [PubMed:17003850 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Mo SL, Zhou ZW, Yang LP, Wei MQ, Zhou SF: New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126. [PubMed:20167001 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein homodimerization activity
Specific Function:
Isoform 1 catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine). Isoform 2 and isoform 3 lack enzyme activity.
Gene Name:
ASMT
Uniprot ID:
P46597
Molecular Weight:
38452.51 Da
References
  1. Minneman KP, Wurtman RJ: The pharmacology of the pineal gland. Annu Rev Pharmacol Toxicol. 1976;16:33-51. [PubMed:180879 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Tryptophan 2,3-dioxygenase activity
Specific Function:
Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses (PubMed:25691885). Tryptophan shortage inhibits T l...
Gene Name:
IDO1
Uniprot ID:
P14902
Molecular Weight:
45325.89 Da
References
  1. Ferry G, Ubeaud C, Lambert PH, Bertin S, Coge F, Chomarat P, Delagrange P, Serkiz B, Bouchet JP, Truscott RJ, Boutin JA: Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase. Biochem J. 2005 May 15;388(Pt 1):205-15. [PubMed:15636586 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Peroxidase activity
Specific Function:
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.
Gene Name:
MPO
Uniprot ID:
P05164
Molecular Weight:
83867.71 Da
References
  1. Ferry G, Ubeaud C, Lambert PH, Bertin S, Coge F, Chomarat P, Delagrange P, Serkiz B, Bouchet JP, Truscott RJ, Boutin JA: Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase. Biochem J. 2005 May 15;388(Pt 1):205-15. [PubMed:15636586 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Oxygen binding
Specific Function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular Weight:
57882.48 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Ohtsuki S, Asaba H, Takanaga H, Deguchi T, Hosoya K, Otagiri M, Terasaki T: Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain. J Neurochem. 2002 Oct;83(1):57-66. [PubMed:12358729 ]
  2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [PubMed:10224140 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23