Department of Molecular Biosciences, The Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, Stockholm, Sweden.
Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Br J Pharmacol. 2018 Nov;175(21):4072-4082. doi: 10.1111/bph.14121. Epub 2018 Jan 18.
The β -adrenoceptor was initially an attractive target for several pharmaceutical companies due to its high expression in rodent adipose tissue, where its activation resulted in decreased adiposity and improved metabolic outputs (such as glucose handling) in animal models of obesity and Type 2 diabetes. However, several drugs acting at the β -adrenoceptor failed in clinical trials. This was thought to be due to their lack of efficacy at the human receptor. Recently, mirabegron, a β -adrenoceptor agonist with human efficacy, was approved in North America, Europe, Japan and Australia for the treatment of overactive bladder syndrome. There are indications that mirabegron may act at other receptors/targets, but whether they have any clinical relevance is relatively unknown. Besides overactive bladder syndrome, mirabegron may have other uses such as in the treatment of heart failure or metabolic disease. This review gives an overview of the off-target effects of mirabegron and its potential use in the treatment of other diseases.
This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.
β-肾上腺素受体最初是几家制药公司的一个有吸引力的目标,因为它在啮齿动物脂肪组织中的高表达,其激活导致肥胖和 2 型糖尿病动物模型中的脂肪减少和代谢产物(如葡萄糖处理)改善。然而,几种在β-肾上腺素受体上起作用的药物在临床试验中失败了。这被认为是由于它们在人类受体上缺乏疗效。最近,米拉贝隆,一种对人类有效的β-肾上腺素受体激动剂,在北美、欧洲、日本和澳大利亚被批准用于治疗膀胱过度活动症。有迹象表明,米拉贝隆可能作用于其他受体/靶点,但它们是否具有任何临床相关性尚不清楚。除了膀胱过度活动症,米拉贝隆可能还有其他用途,如治疗心力衰竭或代谢性疾病。这篇综述概述了米拉贝隆的非靶点作用及其在治疗其他疾病中的潜在用途。
本文是关于 GPCR 分子药理学的专题部分的一部分。要查看本节中的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc/。