Recent Advances in Mineralocorticoid Receptor Antagonists

Publisher Summary This chapter focuses on recent advances in mineralocorticoid receptor (MR) antagonists. MR is a member of the nuclear hormone receptor superfamily and is structurally related to the progesterone receptor, androgen receptor, estrogen receptor, and glucocorticoid receptor. There is extensive clinical validation for treating hypertension and congestive heart failure with spironolactone and eplerenone, both of which are steroid-based antagonists of MR. These agents have side effects—such as gynecomastia, hyperkalemia, and drug–drug interactions—that limit their safety and effectiveness, thus providing a need for MR antagonists with superior profiles. Recent evidence suggests that MR blockade, when given in combination with standard therapy, reduces proteinuria in patients with renal disorders, such as diabetic nephropathy and chronic kidney disease. The past several years have seen a resurgence in targeting MR for intervention in cardiovascular disease. Given the high rate of occurrence of type 2 diabetes in an aging, overweight population, these diseases represent a potentially huge unmet medical need. MR antagonism is also shown to be cardioprotective, reducing mortality rates among patients recovering from acute myocardial infarction.