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Identification
NameMelatonin
Accession NumberDB01065  (APRD00742, DB08189)
Typesmall molecule
Groupsapproved, nutraceutical
Description

Melatonin is a biogenic amine that is found in animals, plants and microbes. Aaron B. Lerner of Yale University is credited for naming the hormone and for defining its chemical structure in 1958. In mammals, melatonin is produced by the pineal gland. The pineal gland is small endocrine gland, about the size of a rice grain and shaped like a pine cone (hence the name), that is located in the center of the brain (rostro-dorsal to the superior colliculus) but outside the blood-brain barrier. The secretion of melatonin increases in darkness and decreases during exposure to light, thereby regulating the circadian rhythms of several biological functions, including the sleep-wake cycle. In particular, melatonin regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature. Melatonin is also implicated in the regulation of mood, learning and memory, immune activity, dreaming, fertility and reproduction. Melatonin is also an effective antioxidant. Most of the actions of melatonin are mediated through the binding and activation of melatonin receptors. Individuals with autism spectrum disorders (ASD) may have lower than normal levels of melatonin. A 2008 study found that unaffected parents of individuals with ASD also have lower melatonin levels, and that the deficits were associated with low activity of the ASMT gene, which encodes the last enzyme of melatonin synthesis. Reduced melatonin production has also been proposed as a likely factor in the significantly higher cancer rates in night workers.

Structure
Thumb
Synonyms
SynonymLanguageCode
5-methoxy-N-acetyltryptamineNot AvailableNot Available
N-[2-(5-methoxyindol-3-yl)ethyl]acetamideNot AvailableNot Available
N-Acetyl-5-methoxytryptamineNot AvailableNot Available
SaltsNot Available
Brand names
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 mixtures
Brand NameIngredients
Plenovit Melatoninamelatonin + vitamin B6
Categories
CAS number73-31-4
WeightAverage: 232.2783
Monoisotopic: 232.121177766
Chemical FormulaC13H16N2O2
InChI KeyInChIKey=DRLFMBDRBRZALE-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
Mass Specshow(8.2 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIndoles and Derivatives
SubclassTryptamines and Derivatives
Direct parentSerotonins
Alternative parentsIndoles; Anisoles; Alkyl Aryl Ethers; Substituted Pyrroles; Secondary Carboxylic Acid Amides; Carboxylic Acids; Enolates; Polyamines
Substituentsindole; anisole; phenol ether; alkyl aryl ether; benzene; substituted pyrrole; pyrrole; secondary carboxylic acid amide; carboxamide group; ether; carboxylic acid; polyamine; enolate; carboxylic acid derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the serotonins. These are compounds containing a serotonin moiety, which conists of an indole that bears an aminoethyl a position 2 and an hydroxyl group at position 5.
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.
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.
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
    6-Hydroxymelatonin sulfateDetails
    N-Acetyl-5-hydroxytryptamine
      N-Acetyl-5-hydroxytryptamine sulfateDetails
      N-Acetyl-5-hydroxytryptamine
      N-Acetyl-5-hydroxytryptamine glucuronideDetails
      6-Hydroxymelatonin
      6-Hydroxymelatonin glucuronideDetails
      Melatonin
        5-MethoxytryptamineDetails
        5-Methoxytryptamine
          PinolineDetails
          5-Methoxytryptamine
            BufotenineDetails
            Bufotenine
              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
              ADMET
              Predicted ADMET features
              Property Value Probability
              Human Intestinal Absorption + 1.0
              Blood Brain Barrier + 0.9928
              Caco-2 permeable - 0.5536
              P-glycoprotein substrate Substrate 0.6188
              P-glycoprotein inhibitor I Non-inhibitor 0.9569
              P-glycoprotein inhibitor II Non-inhibitor 0.6838
              Renal organic cation transporter Non-inhibitor 0.542
              CYP450 2C9 substrate Non-substrate 0.8231
              CYP450 2D6 substrate Substrate 0.5062
              CYP450 3A4 substrate Substrate 0.6505
              CYP450 1A2 substrate Inhibitor 0.9304
              CYP450 2C9 substrate Non-inhibitor 0.9071
              CYP450 2D6 substrate Inhibitor 0.8084
              CYP450 2C19 substrate Non-inhibitor 0.9025
              CYP450 3A4 substrate Non-inhibitor 0.7194
              CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6803
              Ames test Non AMES toxic 0.9132
              Carcinogenicity Non-carcinogens 0.9498
              Biodegradation Not ready biodegradable 0.8764
              Rat acute toxicity 1.8922 LD50, mol/kg Not applicable
              hERG inhibition (predictor I) Weak inhibitor 0.9631
              hERG inhibition (predictor II) Non-inhibitor 0.5124
              Pharmacoeconomics
              ManufacturersNot Available
              Packagers
              Dosage formsNot Available
              Prices
              Unit descriptionCostUnit
              Melatonin powder45.6USDg
              Melatonin 3 mg tablet0.22USDtablet
              Melatonin 5 mg tablet0.12USDtablet
              Melatonin 5 mg tablet sl0.1USDtablet
              Melatonin sublingual tablet0.09USDtablet
              Melatonin 1 mg tablet0.03USDtablet
              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 solubility1.43e-01 g/lALOGPS
              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 area54.12ChemAxon
              rotatable bond count4ChemAxon
              refractivity66.28ChemAxon
              polarizability25.65ChemAxon
              number of rings2ChemAxon
              bioavailability1ChemAxon
              rule of fiveYesChemAxon
              Ghose filterYesChemAxon
              Veber's ruleNoChemAxon
              MDDR-like ruleNoChemAxon
              Spectra
              Spectra
              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 Reference
              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
              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
              3. Hardeland R: Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2005 Jul;27(2):119-30. Pubmed
              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
              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. Epub 2008 Jan 10. Pubmed
              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
              External Links
              ResourceLink
              KEGG CompoundC01598
              PubChem Compound896
              PubChem Substance46509101
              ChemSpider872
              BindingDB9019
              ChEBI16796
              ChEMBLCHEMBL45
              Therapeutic Targets DatabaseDAP000429
              PharmGKBPA164752558
              IUPHAR1357
              Guide to Pharmacology1357
              HETML1
              Drug Product Database793167
              Drugs.comhttp://www.drugs.com/melatonin.html
              PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/mel_0286.shtml
              WikipediaMelatonin
              ATC CodesN05CH01
              AHFS CodesNot Available
              PDB EntriesNot Available
              FDA labelNot Available
              MSDSshow(72 KB)
              Interactions
              Drug Interactions
              Drug
              NifedipineMelatonin can possibly decrease the effect of nifedipine
              Food InteractionsNot Available

              1. Melatonin receptor type 1A

              Kind: protein

              Organism: Human

              Pharmacological action: yes

              Actions: agonist

              Components

              Name UniProt ID Details
              Melatonin receptor type 1A P48039 Details

              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. Epub 2009 May 19. Pubmed
              2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
              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
              4. Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. Pubmed
              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. Epub 2010 Sep 6. Pubmed
              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 and MT melatonin receptors. Bioorg Med Chem. 2010 Sep 1;18(17):6496-511. Epub 2010 Jul 3. Pubmed
              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. Epub 2009 Dec 4. Pubmed

              2. Melatonin receptor type 1B

              Kind: protein

              Organism: Human

              Pharmacological action: yes

              Actions: agonist

              Components

              Name UniProt ID Details
              Melatonin receptor type 1B P49286 Details

              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. Epub 2009 May 19. Pubmed
              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
              3. Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. Pubmed
              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. Epub 2010 Sep 6. Pubmed
              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 and MT melatonin receptors. Bioorg Med Chem. 2010 Sep 1;18(17):6496-511. Epub 2010 Jul 3. Pubmed
              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. Epub 2009 Dec 4. Pubmed

              3. Estrogen receptor

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: antagonist

              Components

              Name UniProt ID Details
              Estrogen receptor P03372 Details

              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
              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. Epub 2009 Oct 1. Pubmed

              4. Nuclear receptor ROR-beta

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: agonist

              Components

              Name UniProt ID Details
              Nuclear receptor ROR-beta Q92753 Details

              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

              5. Calmodulin

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Components

              Name UniProt ID Details
              Calmodulin P62158 Details

              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
              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. Epub 2009 May 19. Pubmed

              6. Myeloperoxidase

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: inhibitor

              Components

              Name UniProt ID Details
              Myeloperoxidase P05164 Details

              References:

              1. Galijasevic S, Abdulhamid I, Abu-Soud HM: Melatonin is a potent inhibitor for myeloperoxidase. Biochemistry. 2008 Feb 26;47(8):2668-77. Epub 2008 Feb 1. Pubmed

              7. Eosinophil peroxidase

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: inhibitor

              Components

              Name UniProt ID Details
              Eosinophil peroxidase P11678 Details

              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. Epub 2008 Jun 2. Pubmed

              8. Calreticulin

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Components

              Name UniProt ID Details
              Calreticulin P27797 Details

              References:

              1. Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. Pubmed
              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

              9. Acetylserotonin O-methyltransferase

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Components

              Name UniProt ID Details
              Acetylserotonin O-methyltransferase P46597 Details

              References:

              1. Minneman KP, Wurtman RJ: The pharmacology of the pineal gland. Annu Rev Pharmacol Toxicol. 1976;16:33-51. Pubmed

              10. Ribosyldihydronicotinamide dehydrogenase [quinone]

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Components

              Name UniProt ID Details
              Ribosyldihydronicotinamide dehydrogenase [quinone] P16083 Details

              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. Epub 2009 May 19. Pubmed

              1. Cytochrome P450 1A1

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate inhibitor

              Components

              Name UniProt ID Details
              Cytochrome P450 1A1 P04798 Details

              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. Epub 2009 Nov 16. Pubmed
              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
              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. Epub 2009 Nov 24. Pubmed

              2. Cytochrome P450 1A2

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate inhibitor

              Components

              Name UniProt ID Details
              Cytochrome P450 1A2 P05177 Details

              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. Epub 2009 Nov 16. Pubmed
              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
              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. Epub 2009 Nov 24. Pubmed
              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

              3. Cytochrome P450 1B1

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate inhibitor

              Components

              Name UniProt ID Details
              Cytochrome P450 1B1 Q16678 Details

              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. Epub 2009 Nov 16. Pubmed
              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
              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. Epub 2009 Nov 24. Pubmed

              4. Cytochrome P450 2C19

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate

              Components

              Name UniProt ID Details
              Cytochrome P450 2C19 P33261 Details

              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
              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. Epub 2009 Nov 24. Pubmed

              5. Cytochrome P450 2C9

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate

              Components

              Name UniProt ID Details
              Cytochrome P450 2C9 P11712 Details

              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

              6. Acetylserotonin O-methyltransferase

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate

              Components

              Name UniProt ID Details
              Acetylserotonin O-methyltransferase P46597 Details

              References:

              1. Minneman KP, Wurtman RJ: The pharmacology of the pineal gland. Annu Rev Pharmacol Toxicol. 1976;16:33-51. Pubmed

              7. Indoleamine 2,3-dioxygenase 1

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate

              Components

              Name UniProt ID Details
              Indoleamine 2,3-dioxygenase 1 P14902 Details

              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

              8. Myeloperoxidase

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate inhibitor

              Components

              Name UniProt ID Details
              Myeloperoxidase P05164 Details

              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

              9. Cytochrome P450 19A1

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: inhibitor

              Components

              Name UniProt ID Details
              Cytochrome P450 19A1 P11511 Details

              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. Epub 2009 Nov 24. Pubmed

              1. Solute carrier family 22 member 8

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: inhibitor

              Components

              Name UniProt ID Details
              Solute carrier family 22 member 8 Q8TCC7 Details

              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
              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

              Comments
              Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13