Abstract
Depression is a disabling condition which adversely affects a person's family, social and work life, and that is associated with a heavy burden to society. Although the available antidepressants have shown their effectiveness and have greatly improved the prognosis of the disorder, the current management of depression is far from being satisfactory. In the last years, besides the classical research involving serotonin, norepineprine and dopamine, non-monoaminergic mechanisms have been explored in the attempt to discover new antidepressants. One such innovative approach focused on melatonergic system, as melatonin is involved in synchronizing circadian rhythms, which are known to be altered in depression. This narrative review aims to provide a comprehensive overview of different aspects of the melatonergic system, including biochemical and anatomical characteristics, impact on the sleep/wake system, and implications for the treatment of depression. In particular, the observation that melatonin may promote sleep and synchronize the internal clock led to development of high-affinity agonists for melatonin receptors (MT). Agomelatine, a naphthalene bioisostere of melatonin, which combines a potent MT1 and MT2 agonism with 5-HT2C receptor antagonism, has been found to be effective in the treatment of depressive and anxiety symptoms associated with major depression, with rapid and beneficial effects on the regulation of sleep continuity and quality. If substantiated by further evidence, the observation that melatonergic system dysfunctions contribute to the development of depression, as well as that the antidepressant action of agomelatine is linked to its binding properties to MT1/MT2 receptors, might open new avenues for the discovery of antidepressive agents.
Keywords: Agomelatine, antidepressants, arylalkylamine, N-acetyltransferase, depression, melatonin, melatonin receptors, ramalteon, non-monoaminergic mechanisms, anatomical characteristics
Current Medicinal Chemistry
Title: Emerging Targets for the Pharmacological Treatment of Depression: Focus on Melatonergic System
Volume: 19 Issue: 3
Author(s): Mario Catena-Dell'Osso, Donatella Marazziti, Francesco Rotella and Cesario Bellantuono
Affiliation:
Keywords: Agomelatine, antidepressants, arylalkylamine, N-acetyltransferase, depression, melatonin, melatonin receptors, ramalteon, non-monoaminergic mechanisms, anatomical characteristics
Abstract: Depression is a disabling condition which adversely affects a person's family, social and work life, and that is associated with a heavy burden to society. Although the available antidepressants have shown their effectiveness and have greatly improved the prognosis of the disorder, the current management of depression is far from being satisfactory. In the last years, besides the classical research involving serotonin, norepineprine and dopamine, non-monoaminergic mechanisms have been explored in the attempt to discover new antidepressants. One such innovative approach focused on melatonergic system, as melatonin is involved in synchronizing circadian rhythms, which are known to be altered in depression. This narrative review aims to provide a comprehensive overview of different aspects of the melatonergic system, including biochemical and anatomical characteristics, impact on the sleep/wake system, and implications for the treatment of depression. In particular, the observation that melatonin may promote sleep and synchronize the internal clock led to development of high-affinity agonists for melatonin receptors (MT). Agomelatine, a naphthalene bioisostere of melatonin, which combines a potent MT1 and MT2 agonism with 5-HT2C receptor antagonism, has been found to be effective in the treatment of depressive and anxiety symptoms associated with major depression, with rapid and beneficial effects on the regulation of sleep continuity and quality. If substantiated by further evidence, the observation that melatonergic system dysfunctions contribute to the development of depression, as well as that the antidepressant action of agomelatine is linked to its binding properties to MT1/MT2 receptors, might open new avenues for the discovery of antidepressive agents.
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Catena-Dell'Osso Mario, Marazziti Donatella, Rotella Francesco and Bellantuono Cesario, Emerging Targets for the Pharmacological Treatment of Depression: Focus on Melatonergic System, Current Medicinal Chemistry 2012; 19 (3) . https://dx.doi.org/10.2174/092986712803414277
DOI https://dx.doi.org/10.2174/092986712803414277 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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