Mineralocorticoid Receptor Blockers: Novel Selective Nonsteroidal Mineralocorticoid Receptor Antagonists. 2020

Daisuke Sueta, and Eiichiro Yamamoto, and Kenichi Tsujita
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto City, 860-8556, Japan. sueta-d@kumamoto-u.ac.jp.

Recently, nonsteroidal mineralocorticoid receptor (MR) antagonists (MRAs), which have been proposed to be called MR blockers (MRBs), have become available for clinical use, but their clinical role is unknown. We reviewed the clinical roles of MRAs and MRBs based on previous knowledge and as demonstrated in representative clinical trials. Steroidal MRAs, such as spironolactone and eplerenone, inhibit the action of aldosterone and cortisol in MRs expressed in several organs and cell types, and accumulating clinical studies have revealed that they exert hypotensive and cardiorenal protective effects. Recently, MRBs, including finerenone and esaxerenone, have been developed and are expected to lower the risk of hyperkalemia, which is common when steroidal MRAs are used. Although the differences between MRAs and MRBs in clinical practice have not yet been established, further studies in this field are expected to broaden our understanding. MRBs exert antihypertensive and cardiorenal protective effects, and their potency is thought to be far superior to that of MRAs, because MRBs have both strong MR inhibitory action and high selectivity. Thus, MRBs could be a promising agent for the treatment of hypertension and cardiorenal, cerebral, and metabolic disorders.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D006333 Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION. Cardiac Failure,Heart Decompensation,Congestive Heart Failure,Heart Failure, Congestive,Heart Failure, Left-Sided,Heart Failure, Right-Sided,Left-Sided Heart Failure,Myocardial Failure,Right-Sided Heart Failure,Decompensation, Heart,Heart Failure, Left Sided,Heart Failure, Right Sided,Left Sided Heart Failure,Right Sided Heart Failure
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077545 Eplerenone A spironolactone derivative and selective ALDOSTERONE RECEPTOR antagonist that is used in the management of HYPERTENSION and CONGESTIVE HEART FAILURE, post-MYOCARDIAL INFARCTION. 9,11-Epoxy-7-(methoxycarbonyl)-3-oxo-17-pregn-4-ene-21,17-carbolactone,Eplerenon,Inspra
D000451 Mineralocorticoid Receptor Antagonists Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE. Aldosterone Antagonist,Aldosterone Antagonists,Aldosterone Receptor Antagonist,Mineralocorticoid Antagonist,Mineralocorticoid Receptor Antagonist,Aldosterone Receptor Antagonists,Mineralocorticoid Antagonists,Antagonist, Aldosterone,Antagonist, Aldosterone Receptor,Antagonist, Mineralocorticoid,Antagonist, Mineralocorticoid Receptor,Antagonists, Aldosterone,Antagonists, Aldosterone Receptor,Antagonists, Mineralocorticoid,Antagonists, Mineralocorticoid Receptor,Receptor Antagonist, Aldosterone,Receptor Antagonist, Mineralocorticoid,Receptor Antagonists, Aldosterone,Receptor Antagonists, Mineralocorticoid
D013148 Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827) Spirolactone,Aldactone,Aldactone A,Aquareduct,Duraspiron,Espironolactona Alter,Espironolactona Mundogen,Flumach,Frumikal,Jenaspiron,Novo-Spiroton,Practon,SC-9420,Spiractin,Spiro L.U.T.,Spiro Von Ct,Spirobeta,Spirogamma,Spirolang,Spirono-Isis,Spironone,Spirospare,Veroshpiron,Verospiron,Verospirone,Ct, Spiro Von,Novo Spiroton,NovoSpiroton,SC 9420,SC9420,Spirono Isis,Von Ct, Spiro
D018161 Receptors, Mineralocorticoid Cytoplasmic proteins that specifically bind MINERALOCORTICOIDS and mediate their cellular effects. The receptor with its bound ligand acts in the nucleus to induce transcription of specific segments of DNA. Mineralocorticoid Receptors,Aldosterone Receptor,Aldosterone Receptors,Corticoid I Receptor,Corticoid Type I Receptors,Mineralocorticoid Receptor,Receptors, Aldosterone,Receptors, Corticoid I,Receptors, Corticoid Type I,Receptors, Mineralocorticoids,Corticoid I Receptors,Mineralocorticoids Receptors,Receptor, Aldosterone,Receptor, Corticoid I,Receptor, Mineralocorticoid

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