Agomelatine

Overview

Agomelatine is a non-peptide small-molecule naphthalene derivative and melatonin analog that acts as an agonist at MT1/MT2 melatonin receptors and antagonist at serotonin 5-HT2C receptors. It is an EMA-approved prescription antidepressant (Valdoxan, approved February 2009 for major depressive disorder in adults) but is NOT FDA-approved in the United States. Post-marketing surveillance identified hepatotoxicity as an important risk, prompting mandatory liver function monitoring and contraindications in hepatic impairment. Despite its prescription status, agomelatine is sold by gray-market vendors as bulk powder labeled 'for research use only.'

Mechanism of Action

Agomelatine acts as a high-affinity agonist at melatonergic MT1 and MT2 receptors and as an antagonist at serotonin 5-HT2C receptors. The two actions are thought to act synergistically—proposed via MT2/5-HT2C receptor heteromers with distinct Gi signaling—to resynchronize circadian rhythms and disinhibit noradrenaline and dopamine release in the frontal cortex, the proposed basis for antidepressant activity.

Research Summary

Agomelatine is an EMA-approved prescription drug for major depressive disorder in adults (approved February 2009, marketed as Valdoxan/Melitor/Thymanax), not an unstudied novel compound. It is NOT FDA-approved in the United States despite completed clinical trials. Pooled human trial data identified hepatotoxicity as an important risk: transaminase elevations >3× upper limit of normal occurred in 1.34% of patients on 25 mg/day and 2.51% on 50 mg/day versus placebo, mostly hepatocellular and idiosyncratic. In rodent studies, chronic agomelatine administration induced regional increases in hippocampal neurogenesis (rat dentate gyrus), normalized stress-suppressed hippocampal neuronal activity and reversed stress-induced decreases in doublecortin expression in chronically stressed rats, and ameliorated stress-induced memory deficits in a mouse chronic social defeat stress model.

Vendors selling Agomelatine

Scored vendors carrying Agomelatine, ranked by trust grade. Grades are computed from indexed Certificates of Analysis. Full $/mg pricing is on the comparison page.

Reported Side Effects

• Hepatotoxicity (transaminase elevations >3× ULN in 1.34–2.51% of patients; mostly hepatocellular, idiosyncratic)
• EMA-mandated liver function monitoring required during treatment
• Contraindicated in hepatic impairment or baseline transaminases >3× ULN
• Very low and variable oral bioavailability (<5%) due to CYP1A2 first-pass metabolism
• Gray-market bulk powder: unverified purity/identity risks independent of clinical hepatotoxicity

Compare Agomelatine with Others

Research References

• Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties.
• Agomelatine: a novel mechanism of antidepressant action involving the melatonergic and the serotonergic system. PMID 18583104.
• Mode of action of agomelatine: synergy between melatonergic and 5-HT2C receptors. PMID 21999473.
• Convergence of Melatonin and Serotonin (5-HT) Signaling at MT2/5-HT2C Receptor Heteromers.

Frequently asked questions

Has Agomelatine been independently lab-tested?

Disclosed Labs has collected 1 Certificate of Analysis (COA) for Agomelatine from 1 independent testing lab. 1 vendor has submitted material for testing. Products average 99.9% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/agomelatine/testing.

Where can researchers source Agomelatine?

1 vendor with Disclosed Labs trust grades currently list Agomelatine, including Kimera Chems. Compare live prices and lab-verified COAs at https://www.disclosedlabs.com/prices/agomelatine.

How does Agomelatine work?

Agomelatine acts as a high-affinity agonist at melatonergic MT1 and MT2 receptors and as an antagonist at serotonin 5-HT2C receptors. The two actions are thought to act synergistically—proposed via MT2/5-HT2C receptor heteromers with distinct Gi signaling—to resynchronize circadian rhythms and disinhibit noradrenaline and dopamine release in the frontal cortex, the proposed basis for antidepressant activity.

What does the research say about Agomelatine?

Agomelatine is an EMA-approved prescription drug for major depressive disorder in adults (approved February 2009, marketed as Valdoxan/Melitor/Thymanax), not an unstudied novel compound. It is NOT FDA-approved in the United States despite completed clinical trials. Pooled human trial data identified hepatotoxicity as an important risk: transaminase elevations >3× upper limit of normal occurred in 1.34% of patients on 25 mg/day and 2.51% on 50 mg/day versus placebo, mostly hepatocellular and idiosyncratic. In rodent studies, chronic agomelatine administration induced regional increases in hippocampal neurogenesis (rat dentate gyrus), normalized stress-suppressed hippocampal neuronal activity and reversed stress-induced decreases in doublecortin expression in chronically stressed rats, and ameliorated stress-induced memory deficits in a mouse chronic social defeat stress model.