The evolution of aldosterone antagonists

Mol Cell Endocrinol. 2004 Mar 31;217(1-2):27-31. doi: 10.1016/j.mce.2003.10.005.


Since the isolation and purification of aldosterone from adrenal extracts 50 years ago (Experientia 9 (1953) 33), scientists have learned a great deal about how and where aldosterone acts, the factors that control its release, what is its role in the pathophysiology of cardiovascular disease, how to make and study aldosterone antagonists, and for what medical purposes these agents are useful. In this paper, we will discuss the evolution of aldosterone antagonists from the relatively nonselective spironolactone (Aldactone), to the highly selective eplerenone (Inspra). Eplerenone represents a molecule with improved steroid receptor selectivity and pharmacokinetic properties in man compared to spironolactone. Recent clinical results have demonstrated that these improvements translate into tolerability and efficacy in patients with cardiovascular disease.

Publication types

  • Historical Article

MeSH terms

  • Aldosterone / history
  • Aldosterone / metabolism
  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism
  • Clinical Trials as Topic
  • Eplerenone
  • Gynecomastia / drug therapy
  • Gynecomastia / metabolism
  • History, 20th Century
  • Humans
  • Mineralocorticoid Receptor Antagonists* / chemical synthesis
  • Mineralocorticoid Receptor Antagonists* / history
  • Mineralocorticoid Receptor Antagonists* / pharmacokinetics
  • Mineralocorticoid Receptor Antagonists* / therapeutic use
  • Spironolactone / analogs & derivatives*
  • Spironolactone / chemical synthesis
  • Spironolactone / history
  • Spironolactone / pharmacokinetics
  • Spironolactone / therapeutic use


  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Aldosterone
  • Eplerenone