Cheng C-J, Rodan A R, Huang C-L
Department of Medicine, Division of Nephrology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan.
Department of Medicine, Division of Nephrology, University of Utah, Salt Lake City, Utah, USA.
Clin Pharmacol Ther. 2017 Sep;102(3):420-435. doi: 10.1002/cpt.754. Epub 2017 Jul 10.
Diuretics are commonly prescribed for treatment in patients with hypertension, edema, or heart failure. Studies on hypertensive and salt-losing disorders and on urea transporters have contributed to better understanding of mechanisms of renal salt and water reabsorption and their regulation. Proteins involved in the regulatory pathways are emerging targets for diuretic and aquaretic therapy. Integrative high-throughput screening, protein structure analysis, and chemical modification have identified promising agents for preclinical testing in animals. These include WNK-SPAK inhibitors, ClC-K channel antagonists, ROMK channel antagonists, and pendrin and urea transporter inhibitors. We discuss the potential advantages and side effects of these potential diuretics.
利尿剂常用于治疗高血压、水肿或心力衰竭患者。对高血压和失盐性疾病以及尿素转运体的研究有助于更好地理解肾脏盐和水重吸收的机制及其调节。参与调节途径的蛋白质正成为利尿剂和利水药治疗的新靶点。整合高通量筛选、蛋白质结构分析和化学修饰已确定了有前景的药物用于动物的临床前测试。这些药物包括WNK-SPAK抑制剂、ClC-K通道拮抗剂、ROMK通道拮抗剂以及pendrin和尿素转运体抑制剂。我们讨论了这些潜在利尿剂的潜在优势和副作用。
