Agomelatine
Explore a selection of our essential drug information below, or:
Identification
- Brand Names
- Valdoxan
- Generic Name
- Agomelatine
- DrugBank Accession Number
- DB06594
- Background
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
- 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Major depressive episode •••••••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
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 Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Agomelatine is combined with 1,2-Benzodiazepine. Abametapir 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. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Agomelatine. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Melitor (Servier Laboratories Ltd.) / Valdoxan (Servier Laboratories Ltd.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Thymanax Tablet 25 mg Oral Servier (Ireland) Industries Limited 2020-12-16 2006-07-27 EU Thymanax Tablet 25 mg Oral Servier (Ireland) Industries Limited 2020-12-16 2006-07-27 EU Thymanax Tablet 25 mg Oral Servier (Ireland) Industries Limited 2020-12-16 2006-07-27 EU Thymanax Tablet 25 mg Oral Servier (Ireland) Industries Limited 2020-12-16 2006-07-27 EU Thymanax Tablet 25 mg Oral Servier (Ireland) Industries Limited 2020-12-16 2006-07-27 EU
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
- 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
- Affected organisms
- 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(CCNC(C)=O)C=CC=C2C=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. [Article]
- 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. [Article]
- 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. [Article]
- 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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Depressive Disorder 1 somestatus stop reason just information to hide Not Available Completed Not Available Fibromyalgia / Major Depressive Disorder (MDD) 1 somestatus stop reason just information to hide Not Available Completed Not Available Major Depressive Disorder (MDD) 1 somestatus stop reason just information to hide Not Available Withdrawn Health Services Research Major Depressive Disorder (MDD) 1 somestatus stop reason just information to hide 4 Completed Treatment Major Depressive Disorder (MDD) 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 25 MG Tablet, coated Oral 2500000 mg Tablet Oral 25.00000 mg Tablet, film coated Oral Tablet, coated Oral 25 mg 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) -1.6 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 27.24 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
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 163.8426395 predictedDarkChem Lite v0.1.0 [M-H]- 165.6722395 predictedDarkChem Lite v0.1.0 [M-H]- 157.9433 predictedDeepCCS 1.0 (2019) [M+H]+ 163.9252395 predictedDarkChem Lite v0.1.0 [M+H]+ 166.1746395 predictedDarkChem Lite v0.1.0 [M+H]+ 160.3013 predictedDeepCCS 1.0 (2019) [M+Na]+ 163.8415395 predictedDarkChem Lite v0.1.0 [M+Na]+ 165.9691395 predictedDarkChem Lite v0.1.0 [M+Na]+ 166.39444 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:12970106, PubMed:18703043, PubMed:19057895, PubMed:29398112, PubMed:7895773). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:19057895, PubMed:29398112). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:18703043, PubMed:29398112). HTR2C is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:29398112). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29398112). Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelanocortin neurons and the release of CRH that then regulates the release of corticosterone (By similarity). Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress (By similarity). Plays a role in insulin sensitivity and glucose homeostasis (By similarity)
- Specific Function
- 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
- Gene Name
- HTR2C
- Uniprot ID
- P28335
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51804.645 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- High affinity receptor for melatonin. Likely to mediate 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
- Specific Function
- G protein-coupled receptor activity
- 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. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- High affinity receptor for melatonin. Likely to mediate 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
- Specific Function
- G protein-coupled receptor activity
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 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. [Article]
- Manikandan S: Agomelatine: A novel melatonergic antidepressant. J Pharmacol Pharmacother. 2010 Jul;1(2):122-3. doi: 10.4103/0976-500X.72369. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- 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. [Article]
Drug created at March 19, 2008 16:39 / Updated at December 11, 2021 01:26