TY - JOUR
T1 - Drug Insight
T2 - eplerenone, a mineralocorticoid-receptor antagonist
AU - McManus, Frances
AU - McInnes, Gordon T
AU - Connell, John M C
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
U2 - 10.1038/ncpendmet0676
DO - 10.1038/ncpendmet0676
M3 - Article
C2 - 18084345
SN - 1759-5029
VL - 4
SP - 44
EP - 52
JO - Nature Reviews Endocrinology
JF - Nature Reviews Endocrinology
IS - 1
ER -