促肾上腺皮质激素释放因子Ⅰ型受体:抗抑郁药物的新靶标

被引：6

作者：

张晶

张有志

李云峰

机构：

[1] 军事医学科学院毒物药物研究所

来源：

国际药学研究杂志 | 2009年 / 36卷 / 04期

基金：

国家高技术研究发展计划(863计划);

关键词：

抑郁症; 促肾上腺皮质激素释放因子,受体; 下丘脑-垂体-肾上腺轴;

D O I：

10.13220/j.cnki.jipr.2009.04.007

中图分类号：

R96 [药理学];

学科分类号：

100602 ; 100706 ;

摘要：

抑郁和焦虑患者常伴随应激激素调节失常,这与下丘脑神经肽促肾上腺皮质激素释放因子(CRF)和精氨酸加压素分泌过多密切相关。CRF主要通过激动促肾上腺皮质激素释放因子Ⅰ型(CRF1)受体诱导抑郁或焦虑样症状,众多研究表明CRF1受体是新型抗抑郁药的潜在靶标。目前已研发出很多基于此靶标的非肽类小分子化合物,但只有一部分进入临床试验,包括NBI-30775/R121919和NBI-34041等。值得注意的是,此类化合物显效与动物的应激水平和自身焦虑程度有关,即CRF1受体拮抗剂可在不影响下丘脑-垂体-肾上腺轴基础活性情况下对抗CRF介导的病理性应激反应,从而提示其副作用可能较低。总之,小分子CRF1受体拮抗剂可能成为治疗应激相关精神疾病的新方法。本文重点综述CRF1受体作为新靶标在抑郁症治疗中的潜在应用。

引用

页码：241 / 244+271 +271

页数：5

共 10 条

[1] Central CRH system in depression and anxiety — Evidence from clinical studies with CRH 1 receptor antagonists[J] . Florian Holsboer,Marcus Ising.European Journal of Pharmacology . 2008 (2)
[2] Innovative Approaches for the Treatment of Depression: Targeting the HPA Axis[J] . Fiona Thomson,Mark Craighead.Neurochemical Research . 2008 (4)
[3] Innovative Approaches for the Development of Antidepressant Drugs: Current and Future Strategies[J] . Lee E. Schechter,Robert H. Ring,Chad E. Beyer,Zo? A. Hughes,Xavier Khawaja,Jessica E. Malberg,Sharon Rosenzweig-Lipson.NeuroRX . 2005 (4)
[4] Listening to mutant mice: a spotlight on the role of CRF/CRF receptor systems in affective disorders[J] . Martin E. Keck,Frauke Ohl,Florian Holsboer,Marianne B. Müller.Neuroscience and Biobehavioral Reviews . 2005 (4)
[5] Identification of molecules potentially involved in mediating the in vivo actions of the corticotropin-releasing hormone receptor 1 antagonist, NBI30775 (R121919)[J] . Anke Post,Frauke Ohl,Osborne F. X. Almeida,Elisabeth B. Binder,Monika Rücker,Sandra Welt,Elke Binder,Florian Holsboer,Inge Sillaber.Psychopharmacology . 2005 (1)
[6] Getting closer to affective disorders: the role of CRH receptor systems[J] . Marianne B. Müller,Wolfgang Wurst.Trends in Molecular Medicine . 2004 (8)
[7] CRF AND CRF RECEPTORS: Role in Stress Responsivity and Other Behaviors[J] . Tracy L. Bale,Wylie W. Vale.Annual Review of Pharmacology and Toxicology . 2004
[8] Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects[J] . Heike E Künzel,Astrid W Zobel,Thomas Nickel,Nibal Ackl,Manfred Uhr,Annette Sonntag,Marcus Ising,Florian Holsboer.Journal of Psychiatric Research . 2003 (6)
[9] Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders
Holmes, A
Heilig, M
Rupniak, NMJ
Steckler, T
Griebel, G
[J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2003, 24 (11) : 580 - 588
[10] Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: new molecular targets .2 Hauger,RL,Risbrough,V,Brauns,O,Dautzenberg,FM. CNS Neurol Disord Drug Targets . 2006

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