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抗抑郁药物研发的新方法。

Fresh approaches to antidepressant drug discovery.

作者信息

Anacker Christoph

机构信息

McGill University, Douglas Mental Health University Institute , 6875 Boulevard La Salle, Montreal, Quebec, H4H 1R3 , Canada +1 514 761 6131 - 2503 ;

出版信息

Expert Opin Drug Discov. 2014 Apr;9(4):407-21. doi: 10.1517/17460441.2014.892071. Epub 2014 Mar 3.

DOI:10.1517/17460441.2014.892071
PMID:24588262
Abstract

INTRODUCTION

The success of antidepressant research has long been challenged by a limited mechanistic understanding of depression pathogenesis and antidepressant treatment response. Progress in this field has thereby consistently been hindered by a lack of novel conceptual approaches and sophisticated experimental techniques to dissect the highly intricate neurobiology of depression. Using fresh approaches to investigate the cellular and molecular mechanisms underlying depression will thus be vital for discovery of novel antidepressant targets.

AREAS COVERED

This article provides an overview of some fundamental problems that depression research is currently facing and critically evaluates how these issues could be addressed by future research. It also discusses novel conceptual and technological advances in the field of neuroscience, particularly in regard to how they may help in providing unprecedented insight into the molecular mechanisms of depression pathogenesis.

EXPERT OPINION

Although progress in antidepressant drug discovery has been limited over recent years, modern innovations in neuroscience, molecular biology, genetics and bioinformatics are just beginning to revolutionize depression research and to reveal novel and promising treatment targets. Integrating findings from a range of relevant experimental models and using the most advanced technology will be vital for the future success of antidepressant drug discovery.

摘要

引言

长期以来,对抗抑郁药研究的成功一直存在挑战,原因在于对抑郁症发病机制和抗抑郁治疗反应的机制理解有限。因此,该领域的进展一直受到缺乏新颖概念方法和复杂实验技术的阻碍,这些技术用于剖析抑郁症高度复杂的神经生物学。采用新方法研究抑郁症潜在的细胞和分子机制对于发现新的抗抑郁靶点至关重要。

涵盖领域

本文概述了抑郁症研究目前面临的一些基本问题,并批判性地评估了未来研究如何解决这些问题。还讨论了神经科学领域的新颖概念和技术进展,特别是它们如何有助于以前所未有的方式洞察抑郁症发病机制的分子机制。

专家观点

尽管近年来抗抑郁药物研发进展有限,但神经科学、分子生物学、遗传学和生物信息学的现代创新才刚刚开始彻底改变抑郁症研究,并揭示新的、有前景的治疗靶点。整合一系列相关实验模型的研究结果并使用最先进的技术对于未来抗抑郁药物研发的成功至关重要。

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Fresh approaches to antidepressant drug discovery.抗抑郁药物研发的新方法。
Expert Opin Drug Discov. 2014 Apr;9(4):407-21. doi: 10.1517/17460441.2014.892071. Epub 2014 Mar 3.
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The neurobiology of depression and antidepressant action.抑郁症的神经生物学与抗抑郁作用。
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Animal inflammation-based models of depression and their application to drug discovery.基于动物炎症的抑郁症模型及其在药物发现中的应用。
Expert Opin Drug Discov. 2017 Oct;12(10):995-1009. doi: 10.1080/17460441.2017.1362385. Epub 2017 Aug 17.
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Antidepressant action: to the nucleus and beyond.抗抑郁作用:从细胞核到更广泛的范围。
Trends Pharmacol Sci. 2005 Dec;26(12):631-8. doi: 10.1016/j.tips.2005.10.005. Epub 2005 Oct 21.
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Could the underestimation of bipolarity obstruct the search for novel antidepressant drugs?双相障碍被低估,会阻碍新型抗抑郁药物的研发吗?
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Molecular Neurobiology and Promising New Treatment in Depression.分子神经生物学与抑郁症有前景的新疗法
Int J Mol Sci. 2016 Mar 15;17(3):381. doi: 10.3390/ijms17030381.
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