Abstract
In the last decades, no significant paradigm shifts in the psychopharmacology of major depressive disorder (MDD) have occurred. In fact, after the serendipitous discovery of the first antidepressant, the poor understanding of the pathophysiology of the illness has deeply limited the development of novel antidepressant agents. Although the discovery of the selective serotonin reuptake inhibitors and the dual-acting serotonin/norepinephrine reuptake inhibitors allowed to improve the treatment of MDD, there are still important unmet clinical needs, as the long latency of antidepressant action, the presence of relevant side effects and the lack of efficacy. In fact, even though the available antidepressants have consistently improved the prognosis of the disorder, the pharmacological treatment of MDD is far from being satisfactory and the disorder remains one of the major causes of morbidity and disability worldwide. Recently, besides the classical research involving the monoamines, other non-monoaminergic molecular mechanisms have been explored in search of new antidepressants. Amongst them, the investigation of the central neuropeptides, including substance P, corticotropinreleasing factor, neuropeptide Y, vasopressin and oxytocin, galanin and melanin-concentrating hormone, is increasingly attracting the attention of researchers worldwide. A number of novel compounds acting on neuropeptide receptors have been developed and tested in both animals and humans with different results. In this review, we provided a synthetic overview of the main neuropeptides, going through biochemical and molecular aspects up to preclinical and clinical evidence which link these molecules to the presence of MDD.
Keywords: Antidepressants, corticotropin-releasing factor receptor antagonists, galanin, major depressive disorder, neurokinin receptor antagonists, nemifitide, neuropeptides, vasopressin receptor antagonists
Mini-Reviews in Medicinal Chemistry
Title:Non-Monoaminergic Targets for the Development of Antidepressants: Focus on Neuropeptides
Volume: 13 Issue: 1
Author(s): Mario Catena-Dell’Osso, Andrea Fagiolini, Donatella Marazziti, Stefano Baroni and Cesario Bellantuono
Affiliation:
Keywords: Antidepressants, corticotropin-releasing factor receptor antagonists, galanin, major depressive disorder, neurokinin receptor antagonists, nemifitide, neuropeptides, vasopressin receptor antagonists
Abstract: In the last decades, no significant paradigm shifts in the psychopharmacology of major depressive disorder (MDD) have occurred. In fact, after the serendipitous discovery of the first antidepressant, the poor understanding of the pathophysiology of the illness has deeply limited the development of novel antidepressant agents. Although the discovery of the selective serotonin reuptake inhibitors and the dual-acting serotonin/norepinephrine reuptake inhibitors allowed to improve the treatment of MDD, there are still important unmet clinical needs, as the long latency of antidepressant action, the presence of relevant side effects and the lack of efficacy. In fact, even though the available antidepressants have consistently improved the prognosis of the disorder, the pharmacological treatment of MDD is far from being satisfactory and the disorder remains one of the major causes of morbidity and disability worldwide. Recently, besides the classical research involving the monoamines, other non-monoaminergic molecular mechanisms have been explored in search of new antidepressants. Amongst them, the investigation of the central neuropeptides, including substance P, corticotropinreleasing factor, neuropeptide Y, vasopressin and oxytocin, galanin and melanin-concentrating hormone, is increasingly attracting the attention of researchers worldwide. A number of novel compounds acting on neuropeptide receptors have been developed and tested in both animals and humans with different results. In this review, we provided a synthetic overview of the main neuropeptides, going through biochemical and molecular aspects up to preclinical and clinical evidence which link these molecules to the presence of MDD.
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Catena-Dell’Osso Mario, Fagiolini Andrea, Marazziti Donatella, Baroni Stefano and Bellantuono Cesario, Non-Monoaminergic Targets for the Development of Antidepressants: Focus on Neuropeptides, Mini-Reviews in Medicinal Chemistry 2013; 13 (1) . https://dx.doi.org/10.2174/1389557511307010002
DOI https://dx.doi.org/10.2174/1389557511307010002 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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