title: Mode of action of agomelatine: synergy between melatonergic and 5-HT2C receptors.
abstract: OBJECTIVE
  The association between depression and circadian rhythm disturbances is well established and successful treatment of depressed patients is accompanied by restoration of circadian rhythms. The new antidepressant agomelatine is an agonist of melatonergic MT₁/MT₂ receptors as well as an antagonist of serotonergic 5-HT2C receptors. Animal studies showed that agomelatine resynchronizes disturbed circadian rhythms and reduces depression-like behaviour.
  
  
  METHODS
  This review analyzes results from different experimental studies.
  
  
  RESULTS
  Recent data on the effects of agomelatine on cellular processes involved in antidepressant mechanisms have shown that the drug is able to increase the expression of brain-derived neurotrophic factor in prefrontal cortex and hippocampus, as well as the expression of activity-regulated cytoskeleton associated protein (Arc) in the prefrontal cortex. In line with this, prolonged treatment with agomelatine increases neurogenesis within the hippocampus, particularly via enhancement of neuronal cell survival. Agomelatine attenuates stress-induced glutamate release in the prefrontal/frontal cortex. Treatment with 5-HT2C antagonists or melatonin alone failed to reproduce these effects.
  
  
  CONCLUSIONS
  The unique mode of action of agomelatine may improve the management of major depression by counteracting the pathogenesis of depression at cellular level, thereby relieving the symptoms of depression. These effects are suggested to be due to a synergistic action on MT₁/MT₂ and 5-HT2C receptors.
authors: Center of Neuropharmacology, Department of Pharmacological Sciences, University of Milan, Milan, Italy. giorgio.racagni@unimi.it
authors: Giorgio
authors: G
authors: Racagni
authors: Marco Andrea
authors: MA
authors: Riva
authors: Raffaella
authors: R
authors: Molteni
authors: Laura
authors: L
authors: Musazzi
authors: Francesca
authors: F
authors: Calabrese
authors: Maurizio
authors: M
authors: Popoli
authors: Daniela
authors: D
authors: Tardito
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D044094:Receptors, Melatonin / Q000819:agonists*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D044405:Receptor, Serotonin, 5-HT2C; D044094:Receptors, Melatonin; D058830:Serotonin 5-HT2 Receptor Antagonists; C084711:agomelatine; D009281:Naphthalenes