Dipartimento di Farmacia, Università di Pisa, Pisa, Italy.
Curr Med Chem. 2018;25(23):2627-2636. doi: 10.2174/0929867324666171012120937.
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.
在过去的四十年中，目前可用于临床的几类利尿剂一直是治疗广泛的心血管和非心血管疾病的一线选择。利尿剂药物通常表现出整体有利的风险/获益平衡。然而，它们并非没有副作用。特别是，所有类别的利尿剂都会引起钾稳态的改变。近年来，对肾脏外髓质钾 (ROMK) 通道的生理作用的理解，为开发一类新型利尿剂提供了一个有趣的药理靶点：ROMK 抑制剂。这种新型药物有望促进利尿剂活性，与临床使用的最有效药物（如呋塞米）相当（甚至更高），对钾稳态的影响有限。在这篇综述中，报告了 ROMK 通道在肾功能中的生理药理学作用，以及目前作为 ROMK 抑制剂开发的最具代表性的分子。
