Hervieu Guillaume J
GlaxoSmithKline R&D, Neurology Centre of Excellence for Drug Discovery, NFSP-North, HW1713 Building H17, L1-130 C06 Third Avenue, Harlow, Essex CM19 5AW, UK.
Expert Opin Ther Targets. 2006 Apr;10(2):211-29. doi: 10.1517/14728222.10.2.211.
Melanin-concentrating hormone (MCH) is a critical hypothalamic anabolic neuropeptide, with key central and peripheral actions on energy balance regulation. The actions of MCH are, so far, known to be transduced through two seven-transmembrane-like receptor paralogues, named MCH1R and MCH2R. MCH2R is not functional in rodents. MCH1R is an important receptor involved in mediating feeding behaviour modulation by MCH in rodents. Pharmacological antagonism at MCH1R in rodents diminishes food intake and results in significant and sustained weight loss in fat tissues, particularly in obese animals. Additionally, MCH1R antagonists have been shown to have anxiolytic and antidepressant properties. The purpose of this review is to highlight the recent numerous pieces of evidence showing that pharmacological blockade at MCH1R could be a potential treatment for obesity and its related metabolic syndrome, as well as for various psychiatric disorders.
促黑素(MCH)是一种关键的下丘脑合成代谢神经肽,在能量平衡调节方面具有重要的中枢和外周作用。迄今为止,已知MCH的作用是通过两个七跨膜样受体旁系同源物介导的,分别称为MCH1R和MCH2R。MCH2R在啮齿动物中无功能。MCH1R是参与介导啮齿动物中MCH对摄食行为调节的重要受体。对啮齿动物的MCH1R进行药理拮抗可减少食物摄入量,并导致脂肪组织显著且持续的体重减轻,尤其是在肥胖动物中。此外,MCH1R拮抗剂已被证明具有抗焦虑和抗抑郁特性。本综述的目的是强调最近的大量证据表明,对MCH1R进行药理阻断可能是治疗肥胖及其相关代谢综合征以及各种精神疾病的潜在方法。