Details of the Drug

General Information of Drug (ID: DMKWFBT)

Drug Name
Melatonin
Synonyms
73-31-4; Melatonine; N-Acetyl-5-methoxytryptamine; Circadin; 5-Methoxy-N-acetyltryptamine; N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide; N-(2-(5-Methoxy-1H-indol-3-yl)ethyl)acetamide; Melatol; Melovine; Melatonex; N-[2-(5-methoxyindol-3-yl)ethyl]acetamide; Acetamide, N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-; UNII-JL5DK93RCL; N-(2-(5-Methoxyindol-3-yl)ethyl)acetamide; N-acetyl-5-methoxy-tryptamine; NSC 113928; CCRIS 3472; CHEMBL45; EINECS 200-797-7; JL5DK93RCL; Acetamide, N-(2-(5-methoxyindol-3-yl)ethyl)-; BRN 0205542; Circadin; Melapure; Melatonina; Posidorm; Vivitas; Night Rest; Pineal Hormone; Revital Melatonin; Rx Balance; Sleep Right; IN1244; M 5250; M1105; ML1; MT6; TNP00300; M-1200; M-1250; Mela-T; Melatonex, Melatonin; Melatonina (TN); NMR/14327425; Nature'S Harmony; PREVENTION 2 (MELATONIN); PREVENTION 3 (MELATONIN); PREVENTION 4 (MELATONIN); PREVENTION 5 (MELATONIN); PREVENTION 1 (MELATONIN) (PREVENTION 1); Acetamide, {N-[2-(5-methoxyindol-3-yl)ethyl]-}; Acetamide, N-[2-(5-methoxyindol-3-yl)ethyl]-(6CI,8CI); N-[2-(5-Methoxy-1H-indol-3-yl)-ethyl]-acetamide; Acetamide, N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-(9CI); Acetamide, {N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-}; Acetamide, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-(9CI); 4-ACETAMIDO-4'-ISOTHIO-CYANATOSTILBENE-2,2'-DISULFONIC ACID; [3H]melatonin; N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide
Indication
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [1]
Insomnia 7A00-7A0Z Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2/3 [3]
Sleep disorder, initiating and maintaining sleep N.A. Investigative [4]
Therapeutic Class
Central Nervous System Stimulants
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 232.28
Logarithm of the Partition Coefficient (xlogp) 0.8
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [5]
Clearance
The drug present in the plasma can be removed from the body at the rate of 16.5 mL/min/kg [6]
Half-life
The concentration or amount of drug in body reduced by one-half in 35 - 50 minutes [6]
Metabolism
The drug is metabolized via the hepatic []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.35861 micromolar/kg/day [7]
Unbound Fraction
The unbound fraction of drug in plasma is 0.39% [6]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.1 L/kg [6]
Water Solubility
The ability of drug to dissolve in water is measured as 0.1 mg/mL [5]
Chemical Identifiers
Formula
C13H16N2O2
IUPAC Name
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide
Canonical SMILES
CC(=O)NCCC1=CNC2=C1C=C(C=C2)OC
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)
InChIKey
DRLFMBDRBRZALE-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
896
ChEBI ID
CHEBI:16796
CAS Number
73-31-4
DrugBank ID
DB01065
TTD ID
D0AN7B
INTEDE ID
DR1018
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Melatonin receptor type 1A (MTNR1A) TT0WAIE MTR1A_HUMAN Binder [8]
Quinone reductase 2 (NQO2) TTJLP0R NQO2_HUMAN Inhibitor [9]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [10]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Substrate [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [12]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [13]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Substrate [11]
Indoleamine 2,3-dioxygenase 1 (IDO1) DE43MW5 I23O1_HUMAN Substrate [14]
Hydroxyindole O-methyltransferase (ASMT) DEHGR57 ASMT_HUMAN Substrate [15]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Gene/Protein Processing [16]
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Gene/Protein Processing [17]
Aggrecan core protein (ACAN) OTUOCW8K PGCA_HUMAN Gene/Protein Processing [17]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Gene/Protein Processing [17]
Alternative prion protein (PRNP) OTE85L1Q APRIO_HUMAN Gene/Protein Processing [18]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [16]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [16]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Gene/Protein Processing [19]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Gene/Protein Processing [16]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Post-Translational Modifications [20]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Melatonin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Obeticholic acid DM3Q1SM Minor Decreased metabolism of Melatonin caused by Obeticholic acid mediated inhibition of CYP450 enzyme. Autoimmune liver disease [DB96] [21]
Ofloxacin DM0VQN3 Minor Decreased metabolism of Melatonin caused by Ofloxacin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [21]
Esterified estrogens DM9KZDO Minor Decreased metabolism of Melatonin caused by Esterified estrogens mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [21]
Alpelisib DMEXMYK Moderate Increased metabolism of Melatonin caused by Alpelisib mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [22]
Quinestrol DMJ6H1Z Minor Decreased metabolism of Melatonin caused by Quinestrol mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [21]
Mestranol DMG3F94 Minor Decreased metabolism of Melatonin caused by Mestranol mediated inhibition of CYP450 enzyme. Contraceptive management [QA21] [21]
Osilodrostat DMIJC9X Minor Decreased metabolism of Melatonin caused by Osilodrostat mediated inhibition of CYP450 enzyme. Cushing syndrome [5A70] [21]
[3H]estrone-3-sulphate DMGPF0N Minor Decreased metabolism of Melatonin caused by [3H]estrone-3-sulphate mediated inhibition of CYP450 enzyme. Discovery agent [N.A.] [21]
Teriflunomide DMQ2FKJ Moderate Increased metabolism of Melatonin caused by Teriflunomide mediated induction of CYP450 enzyme. Hyper-lipoproteinaemia [5C80] [21]
Givosiran DM5PFIJ Minor Decreased metabolism of Melatonin caused by Givosiran mediated inhibition of CYP450 enzyme. Inborn porphyrin/heme metabolism error [5C58] [21]
PF-06463922 DMKM7EW Moderate Increased metabolism of Melatonin caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [21]
Osimertinib DMRJLAT Moderate Increased metabolism of Melatonin caused by Osimertinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [23]
Capmatinib DMYCXKL Minor Decreased metabolism of Melatonin caused by Capmatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [21]
Vemurafenib DM62UG5 Moderate Decreased metabolism of Melatonin caused by Vemurafenib mediated inhibition of CYP450 enzyme. Melanoma [2C30] [24]
Allopregnanolone DMNLHAC Moderate Additive CNS depression effects by the combination of Melatonin and Allopregnanolone. Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z] [25]
Lasmiditan DMXLVDT Moderate Additive CNS depression effects by the combination of Melatonin and Lasmiditan. Migraine [8A80] [26]
Exjade DMHPRWG Moderate Decreased metabolism of Melatonin caused by Exjade mediated inhibition of CYP450 enzyme. Mineral absorption/transport disorder [5C64] [27]
Olaparib DM8QB1D Moderate Increased metabolism of Melatonin caused by Olaparib mediated induction of CYP450 enzyme. Ovarian cancer [2C73] [21]
Rucaparib DM9PVX8 Moderate Decreased metabolism of Melatonin caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [28]
Abametapir DM2RX0I Moderate Decreased metabolism of Melatonin caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [29]
⏷ Show the Full List of 20 DDI Information of This Drug

References

1 Melatonin and its analogs in insomnia and depression. J Pineal Res. 2012 May;52(4):365-75.
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 224).
3 COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020 Jun 1;250:117583.
4 Melatonin in sleep disorders. Neurologia (Engl Ed). 2022 Sep;37(7):575-585.
5 BDDCS applied to over 900 drugs
6 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
8 The human MT1 melatonin receptor stimulates cAMP production in the human neuroblastoma cell line SH-SY5Y cells via a calcium-calmodulin signal transduction pathway. J Neuroendocrinol. 2005 Mar;17(3):170-8.
9 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
10 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.
11 Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005 Apr;33(4):489-94.
12 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.
13 Multiple P450 substrates in a single run: rapid and comprehensive in vitro interaction assay. Eur J Pharm Sci. 2005 Jan;24(1):123-32.
14 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.
15 The pharmacology of the pineal gland. Annu Rev Pharmacol Toxicol. 1976;16:33-51.
16 Melatonin increases the anticancer potential of doxorubicin in Caco-2 colorectal cancer cells. Environ Toxicol. 2021 Jun;36(6):1061-1069. doi: 10.1002/tox.23105. Epub 2021 Jan 28.
17 Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing PPAR expression and enhancing Runx2 expression. J Pineal Res. 2010 Nov;49(4):364-72. doi: 10.1111/j.1600-079X.2010.00803.x. Epub 2010 Aug 24.
18 Co-Administration of Melatonin Effectively Enhances the Therapeutic Effects of Pioglitazone on Mesenchymal Stem Cells Undergoing Indoxyl Sulfate-Induced Senescence through Modulation of Cellular Prion Protein Expression. Int J Mol Sci. 2018 May 4;19(5):1367. doi: 10.3390/ijms19051367.
19 Melatonin inhibits the growth of DMBA-induced mammary tumors by decreasing the local biosynthesis of estrogens through the modulation of aromatase activity. Int J Cancer. 2006 Jan 15;118(2):274-8. doi: 10.1002/ijc.21401.
20 Melatonin prevents nitric oxide-induced apoptosis by increasing the interaction between 14-3-3beta and p-Bad in SK-N-MC cells. J Pineal Res. 2008 Jan;44(1):95-100. doi: 10.1111/j.1600-079X.2007.00494.x.
21 Cerner Multum, Inc. "Australian Product Information.".
22 Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
23 Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
24 Product Information. Zelboraf (vemurafenib). Genentech, South San Francisco, CA.
25 Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
26 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
27 Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
28 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
29 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.