Agomelatine
N06A - Antidepressants
ATC N06AX22
Small molecule
approved 2009
Oral
Natural product
JFDA label: Valdoxan
Mechanism of Action
Agonist of Melatonin receptor — Melatonin receptor agonist; Antagonist of 5-hydroxytryptamine receptor 2C — Serotonin 2c (5-HT2c) receptor antagonist
| Target | Action | Gene / class |
|---|---|---|
| 5-hydroxytryptamine receptor 2C efficacy | ANTAGONIST | HTR2C |
| Melatonin receptor efficacy | AGONIST |
Indications
Approved
- Depressive Disorder — depressive disorder
- Depressive Disorder, Major — major depressive disorder
Off-label
- Anxiety
- Dementia
- Obsessive-Compulsive Disorder
- Schizophrenia
Adverse Reactions
Very Common >10%Common 1–10%Uncommon 0.1–1%
Rare 0.01–0.1%Very Rare <0.01%Not Known
Nervous system disorders (1)
Uncommon Paraesthesia
Hepatobiliary disorders (1)
Rare Hepatitis
Skin and subcutaneous tissue disorders (4)
Uncommon Eczema · Pruritus · Urticaria
Rare Rash erythematous
Eye disorders (1)
Uncommon Vision blurred
Pregnancy & Lactation
Lactation
Caution
Hale L3
A minimal amount of information indicates that exposure and adverse effects can be avoided in breastfed infants if breastfeeding is held for 4 hours after a dose.
Chemistry & Properties
| Formula | C15H17NO2 |
|---|---|
| Molecular weight | 243.31 g/mol |
| IUPAC name | N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide |
| CAS | 138112-76-2 |
| PubChem CID | 82148 |
| InChIKey | YJYPHIXNFHFHND-UHFFFAOYSA-N |
| logP | 2.53 (XLogP 2.7) |
| Polar surface area | 38.33 Ų |
| H-bond acceptors / donors | 2 / 1 |
| Drug-likeness (QED) | 0.90 |
| Lipinski violations | 0 |
SMILES
COc1ccc2cccc(CCNC(C)=O)c2c1Biology & Pharmacokinetics
Pharmacokinetics predicted
| Bioavailability | 70.0% |
|---|---|
| Half-life | 0.688 h |
| Volume of distribution | 0.699 L/kg |
| Protein binding | 87.6% |
| BBB penetrant | No |
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP1A2 | Inhibitor | — |
| CYP1A2 | Substrate | — |
| CYP2C19 | Inhibitor | — |
| CYP2C19 | Substrate | — |
| CYP2C8 | Inhibitor | — |
| CYP2C9 | Substrate | — |
| CYP2D6 | Substrate | — |
| CYP3A4 | Inhibitor | — |
Receptor binding (top 3)
| Target | Action | Affinity |
|---|---|---|
| 5-HT2B receptor (HTR2B) | Antagonist | pKi 6.6 |
| 5-HT2C receptor (HTR2C) | Antagonist | pKi 6.2 |
| 5-HT2A receptor (HTR2A) | Antagonist | pKi 5.4 |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)
Registered Products (1)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Valdoxan | Tablet 25 mg | 28 tab | The Jordan Drugstore Co | 24.080 |