PMID- 22867907 OWN - NLM STAT- MEDLINE DCOM- 20130212 LR - 20220328 IS - 1873-7862 (Electronic) IS - 0924-977X (Linking) VI - 22 Suppl 3 DP - 2012 TI - Synergistic mechanisms involved in the antidepressant effects of agomelatine. PG - S482-6 AB - Agomelatine is a novel and clinically effective antidepressant drug with melatonergic (MT1/MT2) agonist and 5-HT(2C) receptor antagonist properties. Both receptorial components are widely expressed in the central nervous system and it seems that this compound could act synergistically on both the melatonergic and the 5-HT(2C) receptors. In this review we will briefly summarize the preclinical evidence suggesting that the molecular-cellular effects of agomelatine and in turn its antidepressant activity are the result of a synergistic action between its agonism at MT1/MT2 and antagonism at 5-HT(2C) receptors. The antidepressant properties of agomelatine related to its effect on neurogenesis, cell survival, brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeleton associated protein (Arc) and stress-induced glutamate release, appear to be due to this synergistic action. Compared with traditional antidepressants which also affect these parameters, agomelatine is the only one able to resynchronize these effectors at distinct levels, circuital and intracellular. This suggests that agomelatine effects in restoring circadian rhythms and relieving depressive symptoms result from a synergistic interaction between melatonergic and serotonergic receptors. CI - Copyright (c) 2012 Elsevier B.V. and ECNP. All rights reserved. FAU - Tardito, Daniela AU - Tardito D AD - Centro di Neurofarmacologia e Centro di Eccellenza per Malattie Neurodegenerative, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di MIlano, Italy. FAU - Molteni, Raffaella AU - Molteni R FAU - Popoli, Maurizio AU - Popoli M FAU - Racagni, Giorgio AU - Racagni G LA - eng PT - Journal Article PT - Review DEP - 20120804 PL - Netherlands TA - Eur Neuropsychopharmacol JT - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JID - 9111390 RN - 0 (Acetamides) RN - 0 (Antidepressive Agents) RN - 0 (Receptor, Melatonin, MT1) RN - 0 (Receptor, Melatonin, MT2) RN - 0 (Serotonin 5-HT2 Receptor Agonists) RN - 137R1N49AD (agomelatine) SB - IM MH - Acetamides/*therapeutic use MH - Antidepressive Agents/*therapeutic use MH - Depressive Disorder/*drug therapy MH - Humans MH - Receptor, Melatonin, MT1/*agonists MH - Receptor, Melatonin, MT2/*agonists MH - Serotonin 5-HT2 Receptor Agonists/*therapeutic use EDAT- 2012/08/08 06:00 MHDA- 2013/02/13 06:00 CRDT- 2012/08/08 06:00 PHST- 2012/05/23 00:00 [received] PHST- 2012/06/18 00:00 [accepted] PHST- 2012/08/08 06:00 [entrez] PHST- 2012/08/08 06:00 [pubmed] PHST- 2013/02/13 06:00 [medline] AID - S0924-977X(12)00184-8 [pii] AID - 10.1016/j.euroneuro.2012.06.016 [doi] PST - ppublish SO - Eur Neuropsychopharmacol. 2012;22 Suppl 3:S482-6. doi: 10.1016/j.euroneuro.2012.06.016. Epub 2012 Aug 4.