Approaches towards tissue‐selective pharmacology of the mineralocorticoid receptor. (16th December 2021)

• Record Type: Journal Article
• Authors: Clarisse, Dorien; Deng, Lisa; de Bosscher, Karolien; Lother, Achim
• Other Names: Lother Achim guestEditor.; Wenzel Ulrich guestEditor.; Jaisser Frédéric guestEditor.
• Is Part Of: British journal of pharmacology. Volume 179:Number 13(2022)
• Page Start: 3235
• Page End: 3249
• Publication Date: 2021-12-16
• Subjects: drug discovery -- heart failure -- hyperkalemia -- kidney disease -- mineralocorticoid receptor; Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.15719
• Languages: English
• ISSNs: 0007-1188

Abstract

Abstract : Mineralocorticoid receptor antagonists (MRAs) are highly effective therapies for cardiovascular and renal disease. However, the widespread clinical use of currently available MRAs in cardiorenal medicine is hampered by an increased risk of hyperkalaemia. The mineralocorticoid receptor (MR) is a nuclear receptor responsible for fluid and electrolyte homeostasis in epithelial tissues, whereas pathophysiological MR activation in nonepithelial tissues leads to undesirable pro‐inflammatory and profibrotic effects. Therefore, new strategies that selectively target the deleterious effects of the MR but spare its physiological function are needed. In this review, we discuss recent pharmacological developments starting from novel non‐steroidal MRAs, such as finerenone or esaxerenone, that are now entering clinical use, to concepts arising from the current knowledge of the MR signalling pathway, aiming at receptor–coregulator interaction, epigenetics or downstream effectors of the MR. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone‐Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc