Original ArticleFinerenone, a Novel Selective Nonsteroidal Mineralocorticoid Receptor Antagonist Protects From Rat Cardiorenal InjuryKolkhof, Peter PhD*; Delbeck, Martina PhD*; Kretschmer, Axel PhD†; Steinke, Wolfram PhD‡; Hartmann, Elke PhD§; Bärfacker, Lars PhD¶; Eitner, Frank MD*; Albrecht-Küpper, Barbara PhD*; Schäfer, Stefan MD†Author Information Institutes of *Cardiology Research; †Clinical Sciences; ‡Drug Metabolism and Pharmacokinetics; §Toxicology; and ¶Medicinal Chemistry, Bayer HealthCare, Wuppertal, Germany. Reprints: Peter Kolkhof, PhD, Department of Cardiology Research, Global Drug Discovery, Bayer HealthCare, Aprather Weg 18a, 42096 Wuppertal, Germany (e-mail: [email protected]). All authors are employees of Bayer HealthCare. Received January 24, 2014 Accepted February 19, 2014 Journal of Cardiovascular Pharmacology: July 2014 - Volume 64 - Issue 1 - p 69-78 doi: 10.1097/FJC.0000000000000091 Buy Metrics Abstract Pharmacological blockade of the mineralocorticoid receptor (MR) ameliorates end-organ damage in chronic heart failure. However, the clinical use of available steroidal MR antagonists is restricted because of concomitant hyperkalemia especially in patients with diminished kidney function. We have recently identified a novel nonsteroidal MR antagonist, finerenone, which uniquely combines potency and selectivity toward MR. Here, we investigated the tissue distribution and chronic cardiorenal end-organ protection of finerenone in comparison to the steroidal MR antagonist, eplerenone, in 2 different preclinical rat disease models. Quantitative whole-body autoradiography revealed that [14C]-labeled finerenone equally distributes into rat cardiac and renal tissues. Finerenone treatment prevented deoxycorticosterone acetate-/salt-challenged rats from functional as well as structural heart and kidney damage at dosages not reducing systemic blood pressure. Finerenone reduced cardiac hypertrophy, plasma prohormone of brain natriuretic peptide, and proteinuria more efficiently than eplerenone when comparing equinatriuretic doses. In rats that developed chronic heart failure after coronary artery ligation, finerenone (1 mg·kg−1·d−1), but not eplerenone (100 mg·kg−1·d−1) improved systolic and diastolic left ventricular function and reduced plasma prohormone of brain natriuretic peptide levels. We conclude that finerenone may offer end-organ protection with a reduced risk of electrolyte disturbances. © 2014 by Lippincott Williams & Wilkins.