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Record Information
Version4.0
Creation Date2012-09-06 15:16:52 UTC
Update Date2017-09-27 08:28:01 UTC
HMDB IDHMDB0015636
Secondary Accession Numbers
  • HMDB15636
Metabolite Identification
Common NameAgomelatine
DescriptionAgomelatine is structurally closely related to melatonin. Agomelatine is a potent agonist at melatonin receptors and an antagonist at serotonin-2C (5-HT2C) receptors, tested in an animal model of depression. Agomelatine was discovered and developed by the European pharmaceutical company Servier Laboratories Ltd. Servier continue to develop the drug and conduct phase III trials in the European Union. In 2005 Servier submitted Agomelatine to the European Medicines Agency (EMEA). On 27 July 2006 the Committee for Medical Products for Human Use (CHMP) of the EMEA recommended a refusal of the marketing authorisation of Valdoxan/Thymanax. The major concern was that efficacy had not been sufficiently shown. In 2006 Servier sold the rights to develop Agomelatine in the US to Novartis. The development for the US market was discontinued in October 2011. It is currently sold in Australia under the Valdoxan trade name.
Structure
Thumb
Synonyms
ValueSource
ValdoxanKegg
S-20098HMDB
S20098HMDB
N-(2-(7-Methoxy-1-naphthyl)ethyl)acetamideMeSH
ThymanaxMeSH
ago 178MeSH
ago-178MeSH
Chemical FormulaC15H17NO2
Average Molecular Weight243.301
Monoisotopic Molecular Weight243.125928793
IUPAC NameN-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide
Traditional Nameagomelatine
CAS Registry Number138112-76-2
SMILES
COC1=CC2=C(C=CC=C2CCNC(C)=O)C=C1
InChI Identifier
InChI=1S/C15H17NO2/c1-11(17)16-9-8-13-5-3-4-12-6-7-14(18-2)10-15(12)13/h3-7,10H,8-9H2,1-2H3,(H,16,17)
InChI KeyYJYPHIXNFHFHND-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as n-acetyl-2-arylethylamines. These are compounds containing an acetamide group that is N-linked to an arylethylamine.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassCarboxylic acids and derivatives
Direct ParentN-acetyl-2-arylethylamines
Alternative Parents
Substituents
  • N-acetyl-2-arylethylamine
  • Naphthalene
  • Anisole
  • Alkyl aryl ether
  • Benzenoid
  • Secondary carboxylic acid amide
  • Ether
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Role

Industrial application:

  Pharmaceutical industry:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0078 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0078 g/LALOGPS
logP2.83ALOGPS
logP2.04ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)15.96ChemAxon
pKa (Strongest Basic)-0.94ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area38.33 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity71.64 m³·mol⁻¹ChemAxon
Polarizability27.18 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableView in JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-1910000000-17cebfbe6b9845617b5dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udl-0290000000-2f32e7333df35f0d31e0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-1890000000-f8670d6acc856a2aef34View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-103c-1900000000-44f5e0bbe33a080e259bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-1190000000-60e7560fd8d53fc46465View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0zfu-3590000000-b1f2b056df1b588a9894View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052f-9200000000-7d7eb2751fc51b48fda4View in MoNA
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
No entries found
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06594 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06594 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB06594
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID74141
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAgomelatine
METLIN IDNot Available
PubChem Compound82148
PDB IDNot Available
ChEBI ID108209
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Millan MJ, Brocco M, Gobert A, Dekeyne A: Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology (Berl). 2005 Feb;177(4):448-58. Epub 2004 Jul 31. [PubMed:15289999 ]
  2. Racagni G, Riva MA, Popoli M: The interaction between the internal clock and antidepressant efficacy. Int Clin Psychopharmacol. 2007 Oct;22 Suppl 2:S9-S14. [PubMed:17917564 ]
  3. Hardeland R, Poeggeler B, Srinivasan V, Trakht I, Pandi-Perumal SR, Cardinali DP: Melatonergic drugs in clinical practice. Arzneimittelforschung. 2008;58(1):1-10. doi: 10.1055/s-0031-1296459. [PubMed:18368944 ]

Enzymes

General function:
Involved in monooxygenase 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, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
References
  1. Dolder CR, Nelson M, Snider M: Agomelatine treatment of major depressive disorder. Ann Pharmacother. 2008 Dec;42(12):1822-31. doi: 10.1345/aph.1L296. Epub 2008 Nov 25. [PubMed:19033480 ]
General function:
Involved in monooxygenase 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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Carney RM, Shelton RC: Agomelatine for the treatment of major depressive disorder. Expert Opin Pharmacother. 2011 Oct;12(15):2411-9. doi: 10.1517/14656566.2011.607812. [PubMed:21916789 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular weight:
51820.7
References
  1. Millan MJ, Brocco M, Gobert A, Dekeyne A: Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology (Berl). 2005 Feb;177(4):448-58. Epub 2004 Jul 31. [PubMed:15289999 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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:
39374.3
References
  1. Millan MJ, Brocco M, Gobert A, Dekeyne A: Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology (Berl). 2005 Feb;177(4):448-58. Epub 2004 Jul 31. [PubMed:15289999 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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:
40187.9
References
  1. Millan MJ, Brocco M, Gobert A, Dekeyne A: Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology (Berl). 2005 Feb;177(4):448-58. Epub 2004 Jul 31. [PubMed:15289999 ]