摘要
在过去的四十年中,目前可供临床使用的几种利尿剂已成为治疗广泛心血管和非心血管疾病的首选药物。利尿剂一般表现出整体有利的风险/利益平衡。然而,它们并不缺少副作用。特别是所有类别利尿剂均可导致钾稳态的改变。 近年来,通过对肾外髓质钾(ROMK)通道生理作用的研究了解,显示出一个有趣的药理目标可供开发一类创新的利尿剂:ROMK抑制剂。这种新颖类型的药物有望促进利尿剂的活性相当于(甚至高于)在临床上使用的最有效的药物(如呋塞米),同时对钾稳态的影响有限。本文综述了ROMK通道在肾功能中的生理药理作用,以及目前已发展为ROMK抑制剂的最有代表性的分子。
关键词: 肾、髓质钾通道、利尿药、稳态、ROMK
Current Medicinal Chemistry
Title:The Renal Outer Medullary Potassium Channel (ROMK): An Intriguing Pharmacological Target for an Innovative Class of Diuretic Drugs
Volume: 25 Issue: 23
关键词: 肾、髓质钾通道、利尿药、稳态、ROMK
摘要: In the last four decades, the several classes of diuretics, currently available for clinical use, have been the first line option for the therapy of widespread cardiovascular and non-cardiovascular diseases. Diuretic drugs generally exhibit an overall favourable risk/benefit balance. However, they are not devoid of side effects. In particular, all the classes of diuretics cause alteration of potassium homeostasis.
In recent years, understanding of the physiological role of the renal outer medullary potassium (ROMK) channels, has shown an intriguing pharmacological target for developing an innovative class of diuretic agents: the ROMK inhibitors. This novel class is expected to promote diuretic activity comparable to (or even higher than) that provided by the most effective drugs used in clinics (such as furosemide), with limited effects on potassium homeostasis.
In this review, the physio-pharmacological roles of ROMK channels in the renal function are reported, along with the most representative molecules which have been currently developed as ROMK inhibitors.
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The Renal Outer Medullary Potassium Channel (ROMK): An Intriguing Pharmacological Target for an Innovative Class of Diuretic Drugs, Current Medicinal Chemistry 2018; 25 (23) . https://dx.doi.org/10.2174/0929867324666171012120937
DOI https://dx.doi.org/10.2174/0929867324666171012120937 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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