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Drug Insight: eplerenone, a mineralocorticoid-receptor antagonist

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 44–52 (2008)Cite this article

Abstract

Increasing recognition of the role of aldosterone in cardiovascular disease has been supported by a significant body of evidence from animal models. This evidence has been translated into clinical practice, and large-scale, randomized, placebo-controlled trials have confirmed the beneficial effects of mineralocorticoid blockade in patients with heart failure. As a consequence, there has been a resurgence in the use of mineralocorticoid-receptor antagonists in clinical practice that has prompted the search for a potent and specific antagonist without the sexual side effects of spironolactone. Eplerenone, a mineralocorticoid-receptor antagonist with minimal binding to the progesterone and androgen receptors, is now licensed for treatment of heart failure in Europe and heart failure and hypertension in the US; it has also been proposed as a treatment for a variety of cardiovascular conditions. This article reviews the current concepts of the actions of aldosterone at a cellular level. Recent findings regarding its role as a cardiovascular hormone, both in animal models and human studies, are discussed. We also describe the development of mineralocorticoid-receptor blockers following the isolation of aldosterone and discuss the subsequent search for a specific mineralocorticoid antagonist. In addition we detail the effects of eplerenone in a number of clinical situations and outline its potential future applications.

Key Points

  • There is increasing evidence that aldosterone has a key role in cardiovascular pathology

  • Experimental data suggest that mineralocorticoid blockade is beneficial in models of hypertension, nephropathy and heart failure

  • Mineralocorticoid blockade has proved a valuable therapeutic option in clinical studies of heart failure and after myocardial infarction

  • Few data exist regarding outcomes in large cohorts of patients in other cardiovascular conditions (e.g. nephropathy, hypertension) and these are required, as well as confirmatory studies in heart failure, to establish the role of eplerenone in clinical practice

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Figure 1: Structures of mineralocorticoid-receptor antagonists.

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Authors and Affiliations

  1. F McManus is a Medical Research Council Clinical Training Fellow, GT McInnes is Professor of Clinical Pharmacology, and JMC Connell is Professor of Endocrinology, at the University of Glasgow, Glasgow, UK.,

    Frances McManus, Gordon T McInnes & John MC Connell

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Correspondence to John MC Connell.

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McManus, F., McInnes, G. & Connell, J. Drug Insight: eplerenone, a mineralocorticoid-receptor antagonist. Nat Rev Endocrinol 4, 44–52 (2008). https://doi.org/10.1038/ncpendmet0676

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