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Agomelatine
Identification
- Name
- Agomelatine
- Accession Number
- DB06594
- Description
Agomelatine 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 developed in Europe by Servier Laboratories Ltd. and submitted to the European Medicines Agency (EMA) in 2005. The Committee for Medical Products for Human Use (CHMP) recommended refusal of marketing authorization on 27 July 2006. 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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Agomelatine (DB06594)
- Weight
- Average: 243.301
Monoisotopic: 243.125928793 - Chemical Formula
- C15H17NO2
- Synonyms
- Agomelatina
- Agomelatine
- External IDs
- AGO 178
- AGO-178
- AGO178C
- S-20098
- S20098
Pharmacology
- Indication
Agomelatine is indicated to treat major depressive episodes in adults.
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
Agomelatine resynchronises circadian rhythms in animal models of delayed sleep phase syndrome and other circadian rhythm disruptions. It increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin. Agomelatine has shown an antidepressant-like effect in animal depression models, (learned helplessness test, despair test, and chronic mild stress) circadian rhythm desynchronisation, and in stress and anxiety models. In humans, agomelatine has positive phase shifting properties; it induces a phase advance of sleep, body temperature decline and melatonin onset. Controlled studies in humans have shown that agomelatine is as effective as the SSRI antidepressants paroxetine and sertraline in the treatment of major depression
- Mechanism of action
The novel antidepressant agent, agomelatine, behaves as an agonist at melatonin receptors (MT1 and MT2) and as an antagonist at serotonin (5-HT)(2C) receptors.
Target Actions Organism A5-hydroxytryptamine receptor 2C antagonistHumans AMelatonin receptor type 1A agonistHumans AMelatonin receptor type 1B agonistHumans - Absorption
Bioavailability is less than 5%.
- Volume of distribution
- Not Available
- Protein binding
> 95%
- Metabolism
Hepatic (90% CYP1A2 and 10% CYP2C9).
- Route of elimination
- Not Available
- Half-life
<2 hours
- Clearance
- Not Available
- Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
- Not Available
- Affected organisms
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Unlock Additional DataAbametapir The serum concentration of Agomelatine can be increased when it is combined with Abametapir. Abatacept The metabolism of Agomelatine can be increased when combined with Abatacept. Abiraterone The serum concentration of Agomelatine can be increased when it is combined with Abiraterone. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Agomelatine. Acetaminophen The metabolism of Agomelatine can be decreased when combined with Acetaminophen. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Agomelatine. Acetohexamide The metabolism of Acetohexamide can be decreased when combined with Agomelatine. Acetophenazine The risk or severity of adverse effects can be increased when Acetophenazine is combined with Agomelatine. Acetylsalicylic acid The metabolism of Acetylsalicylic acid can be decreased when combined with Agomelatine. Aclidinium Agomelatine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Not Available
Products
- International/Other Brands
- Melitor (Servier Laboratories Ltd.) / Valdoxan (Servier Laboratories Ltd.)
Categories
- ATC Codes
- N06AX22 — Agomelatine
- Drug Categories
- Acetates
- Acids, Acyclic
- Amides
- Antidepressive Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Fatty Acids
- Fatty Acids, Volatile
- Lipids
- Melatonin, agonists
- Nervous System
- Psychoanaleptics
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2C Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Antagonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as n-acetyl-2-arylethylamines. These are compounds containing an acetamide group that is N-linked to an arylethylamine.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Carboxylic acid derivatives
- Direct Parent
- N-acetyl-2-arylethylamines
- Alternative Parents
- Naphthalenes / Anisoles / Alkyl aryl ethers / Secondary carboxylic acid amides / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Alkyl aryl ether / Anisole / Aromatic homopolycyclic compound / Benzenoid / Carbonyl group / Ether / Hydrocarbon derivative / N-acetyl-2-arylethylamine / Naphthalene / Organic nitrogen compound
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- Not Available
Chemical Identifiers
- UNII
- 137R1N49AD
- CAS number
- 138112-76-2
- InChI Key
- YJYPHIXNFHFHND-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide
- SMILES
- COC1=CC2=C(C=CC=C2CCNC(C)=O)C=C1
References
- Synthesis Reference
Jean-Claude Souvie, Isaac Gonzalez Blanco, Gilles Thominot, Genevieve Chapuis, Stephane Horvath, Gerard Damien, "Process for the synthesis and crystalline form of agomelatine." U.S. Patent US20050182276, issued August 18, 2005.
US20050182276- General References
- 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]
- 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]
- 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]
- External Links
- Human Metabolome Database
- HMDB0015636
- KEGG Drug
- D02578
- PubChem Compound
- 82148
- PubChem Substance
- 175427076
- ChemSpider
- 74141
- BindingDB
- 50035179
- ChEBI
- 134990
- ChEMBL
- CHEMBL10878
- ZINC
- ZINC000000005608
- PharmGKB
- PA165958363
- PDBe Ligand
- AWY
- Wikipedia
- Agomelatine
- PDB Entries
- 5q1s / 6me5
- MSDS
- Download (15.5 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Delusional Disorder / Schizoaffective Disorders / Schizophrenia / Schizophrenia-spectrum-disorders 1 4 Completed Treatment Major Depressive Disorder (MDD) 1 4 Not Yet Recruiting Treatment Circadian Rhythm Disorders / Depression / Parkinson's Disease (PD) / Sleep disorders and disturbances 1 4 Unknown Status Treatment Major Depressive Disorder (MDD) 1 3 Completed Prevention Major Depressive Disorder (MDD) 1 3 Completed Treatment Major Depressive Disorder (MDD) 6 3 Terminated Treatment Anxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenia 1 3 Terminated Treatment Major Depressive Disorder (MDD) 1 3 Withdrawn Treatment Depressive Disorder, Treatment-Resistant 1 2 Completed Treatment Obsessive Compulsive Disorder (OCD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, coated Oral 25 mg Tablet, coated 25 mg Tablet Tablet Oral 25 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility ~0.5 mg/ml in 1:1 EtOH:PBS (pH 7.2); ~30 mg/ml in EtOH, DMF & DMSO Not Available - Predicted Properties
Property Value Source Water Solubility 0.00776 mg/mL ALOGPS logP 2.83 ALOGPS logP 2.04 ChemAxon logS -4.5 ALOGPS pKa (Strongest Acidic) 15.96 ChemAxon pKa (Strongest Basic) -0.94 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 38.33 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 71.64 m3·mol-1 ChemAxon Polarizability 27.18 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9923 Caco-2 permeable + 0.7464 P-glycoprotein substrate Substrate 0.5356 P-glycoprotein inhibitor I Non-inhibitor 0.6423 P-glycoprotein inhibitor II Non-inhibitor 0.6412 Renal organic cation transporter Non-inhibitor 0.5291 CYP450 2C9 substrate Non-substrate 0.7647 CYP450 2D6 substrate Substrate 0.7219 CYP450 3A4 substrate Substrate 0.7276 CYP450 1A2 substrate Inhibitor 0.8543 CYP450 2C9 inhibitor Non-inhibitor 0.7758 CYP450 2D6 inhibitor Non-inhibitor 0.5445 CYP450 2C19 inhibitor Non-inhibitor 0.7478 CYP450 3A4 inhibitor Non-inhibitor 0.7746 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5467 Ames test AMES toxic 0.6796 Carcinogenicity Non-carcinogens 0.8958 Biodegradation Not ready biodegradable 0.8296 Rat acute toxicity 2.2095 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9236 hERG inhibition (predictor II) Inhibitor 0.6648
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-000i-1910000000-17cebfbe6b9845617b5d
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
- Gene Name
- HTR2C
- Uniprot ID
- P28335
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51820.705 Da
References
- 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]
- Kind
- Protein
- Organism
- Humans
- 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 ...
- Gene Name
- MTNR1A
- Uniprot ID
- P48039
- Uniprot Name
- Melatonin receptor type 1A
- Molecular Weight
- 39374.315 Da
References
- 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]
- Kind
- Protein
- Organism
- Humans
- 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 ...
- Gene Name
- MTNR1B
- Uniprot ID
- P49286
- Uniprot Name
- Melatonin receptor type 1B
- Molecular Weight
- 40187.895 Da
References
- 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]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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 un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Yasar U: Does celecoxib inhibit agomelatine metabolism via CYP2C9 or CYP1A2? Drug Des Devel Ther. 2018 Jul 11;12:2169-2172. doi: 10.2147/DDDT.S169358. eCollection 2018. [PubMed:30034221]
- Manikandan S: Agomelatine: A novel melatonergic antidepressant. J Pharmacol Pharmacother. 2010 Jul;1(2):122-3. doi: 10.4103/0976-500X.72369. [PubMed:21350627]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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 un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- 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]
Drug created on March 19, 2008 10:39 / Updated on June 12, 2020 10:52
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