{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:54:10Z","timestamp":1791309250322,"version":"4.3.1"},"reference-count":151,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2013,6,13]],"date-time":"2013-06-13T00:00:00Z","timestamp":1371081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melatonin exerts its actions through membrane MT1\/MT2 melatonin receptors, which belong to the super family of G-protein-coupled receptors consisting of the typical seven transmembrane domains. MT1 and MT2 receptors are expressed in various tissues of the body either as single ones or together. A growing literature suggests that the melatonergic system may be involved in the pathophysiology of mood and anxiety disorders. In fact, some core symptoms of depression show disturbance of the circadian rhythm in their clinical expression, such as diurnal mood and other symptomatic variation, or are closely linked to circadian system functioning, such as sleep-wake cycle alterations. In addition, alterations have been described in the circadian rhythms of several biological markers in depressed patients. Therefore, there is interest in developing antidepressants that have a chronobiotic effect (i.e., treatment of circadian rhythm disorders). As melatonin produces chronobiotic effects, efforts have been aimed at developing agomelatine, an antidepressant with melatonin agonist activity. The present paper reviews the role of the melatonergic system in the pathophysiology of mood and anxiety disorders and the clinical characteristics of agomelatine. Implications of agomelatine in \u201creal world\u201d clinical practice will be also discussed.<\/jats:p>","DOI":"10.3390\/ijms140612458","type":"journal-article","created":{"date-parts":[[2013,6,13]],"date-time":"2013-06-13T11:30:15Z","timestamp":1371123015000},"page":"12458-12483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["The Melatonergic System in Mood and Anxiety Disorders and the Role of Agomelatine: Implications for Clinical Practice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4415-5058","authenticated-orcid":false,"given":"Domenico","family":"De Berardis","sequence":"first","affiliation":[{"name":"National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital \"G. Mazzini\", ASL 4 Teramo, Italy"},{"name":"Department of Neuroscience and Imaging, Chair of Psychiatry, University \"G. D'Annunzio\",  Chieti 66013, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Marini","sequence":"additional","affiliation":[{"name":"National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital \"G. Mazzini\", ASL 4 Teramo, Italy"},{"name":"Department of Neuroscience and Imaging, Chair of Psychiatry, University \"G. D'Annunzio\",  Chieti 66013, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Fornaro","sequence":"additional","affiliation":[{"name":"Department of \"Scienze della Formazione\", University of Catania, Catania 95121, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkataramanujam","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Sri Sathya Sai Medical Educational and Research Foundation, Medical Sciences Research Study Center, Prasanthi Nilayam, 40-Kovai Thirunagar Coimbatore, Tamilnadu 641014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Iasevoli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine \"Federico II\", Naples 80131, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Tomasetti","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine \"Federico II\", Naples 80131, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Valchera","sequence":"additional","affiliation":[{"name":"Hermanas Hospitalarias, FoRiPsi, Villa S. Giuseppe Hospital, Ascoli Piceno 63100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Perna","sequence":"additional","affiliation":[{"name":"Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences,  Villa San Benedetto Menni, Albese con Cassano, Como 22032, Italy"},{"name":"Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine,  University of Miami, 33124 Miami, USA"},{"name":"Department of Psychiatry and Neuropsychology, University of Maastricht, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Antonia","family":"Quera-Salva","sequence":"additional","affiliation":[{"name":"AP-HP Sleep Unit, Department of Physiology, Raymond Poincar\u00e9 Hospital, Garches 92380, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Martinotti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Imaging, Chair of Psychiatry, University \"G. D'Annunzio\",  Chieti 66013, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Di Giannantonio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Imaging, Chair of Psychiatry, University \"G. D'Annunzio\",  Chieti 66013, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/217953a0","article-title":"Formation of melatonin and 5-hydroxyindole acetic acid from 14C-tryptophan by rat pineal glands in organ culture","volume":"217","author":"Wurtman","year":"1968","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S1087-0792(98)90020-X","article-title":"Basic aspects of melatonin action","volume":"2","author":"Cardinali","year":"1998","journal-title":"Sleep. Med. 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