A profile of antidepressive effects of agomelatine and a current view on the mechanism of its action

• Published in: Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova Vol. 117; no. 12; p. 124
• Main Authors: Shagiakhmetov, F Sh, Anokhin, P K, Popova, A O, Shamakina, I Yu
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 2017
• Subjects: Acetamides - pharmacology; Antidepressive Agents - pharmacology; Brain-Derived Neurotrophic Factor - blood; Brain-Derived Neurotrophic Factor - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Humans; Receptor, Melatonin, MT2 - agonists; Receptor, Melatonin, MT2 - metabolism; Receptors, Serotonin, 5-HT2 - metabolism; Suprachiasmatic Nucleus - drug effects; Suprachiasmatic Nucleus - metabolism; Synaptic Transmission - drug effects; pharmacodynamics; anhedonia; pharmacology; mechanism of action; agomelatine; clinical profile; functional selectivity
• ISSN: 1997-7298
• DOI: 10.17116/jnevro2017117121124-131

Agomelatine is one of the latest antidepressants (melatoninergic agonists) with a new mechanism of action. From the positions of classical monoaminoergic theory, tts mechanism of action is difficult to understand, because the drug increases the levels of monoamines and neurotrophic factors, while not affecting their reuptake and negative feedback, which control neurotransmission level. Besides the effect on suprachiasmatic nucleus, a relevant role in the mechanism of action of agomelatine plays its special functionally selective (with regard to intracellular signaling pathways) interaction with heteromeric complexes of serotonin 5-НТ2С and melatonin MT2 receptors in the hippocampus and cerebral cortex. Agomelatine is competitive to other modern antidepressants in the efficacy assessed by the percentage of complete responders and superior in the total frequency of remissions. Compared to other SSRI antidepressants, agomelatine is more effective for anhedonia. In these cases, agomelatine increases the level of brain-derived neurotrophic factor (BDNF) in the blood of responders.