The 45-year story of the development of an anti-aldosterone more specific than spironolactone

  title={The 45-year story of the development of an anti-aldosterone more specific than spironolactone},
  author={Jo{\"e}l M{\'e}nard},
  journal={Molecular and Cellular Endocrinology},
  • J. Ménard
  • Published 31 March 2004
  • Medicine, Biology
  • Molecular and Cellular Endocrinology

Mineralocorticoid Receptor Antagonists for Treatment of Hypertension and Heart Failure.

  • D. Sica
  • Medicine, Biology
    Methodist DeBakey cardiovascular journal
  • 2015
Hyperkalemia should always be considered a possibility in patients receiving either spironolactone or eplerenone; therefore, anticipatory steps should be taken to minimize the likelihood of its occurrence if long-term therapy of these agents is being considered.

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development

Novel non-steroidal MRAs such as apararenone, esaxerenone and finerenone are in late-stage clinical trials in patients with heart failure, chronic kidney disease, hypertension and liver disease and the history of the various generations of MRAs is reflected.

A Comparison of the Aldosterone‐blocking Agents Eplerenone and Spironolactone

Both spironolactone and eplerenone effectively treat hypertension and heart failure but comparisons are complicated by the deficiency of head‐to‐head trials and differences between patient populations.

The pharmacological treatment of primary aldosteronism

For the increasing proportion of patients with primary aldosteronism suitable for long-term medical treatment, mineralocorticoid receptor blockade (better tolerated with eplerenone) should be considered the most appropriate choice of treatment, pending the development of better alternatives.

The risks and benefits of aldosterone antagonists

  • D. Sica
  • Medicine, Biology
    Current heart failure reports
  • 2005
For most patients the risk of developing hyperkalemia should not dissuade the prudent clinician from use of spironolactone and eplerenone, but as enthusiasm grows for use of mineralocorticoid-blocking agents, the risks inherent to use of such drugs become more pertinent.

Safety and Efficacy of Eplerenone in the Management of Essential Hypertension

Eplerenone, the selective mineralocorticoid receptor antagonist, is a promising cardiovascular drug licensed for the treatment of heart failure in Europe and heart failure and hypertension in the USA and effectively blocks the mineralocortex receptor without the unpleasant sexual side effect profile of spironolactone.

Eplerenone relieves spironolactone-induced painful gynaecomastia in a patient with primary aldosteronism.

Eplerenone is a highly selective aldosterone antagonist and is the drug of choice for the treatment of primary aldosteronism, but presents sexual side effects, such as impotence, painful gynaecomastia and menstrual disturbances in pre-menopausal women.

A Literature Review of the Pharmacokinetics, Pharmacodynamics, and Possible Uses of Spironolactone

  • J. Khan
  • Biology
    UTSC's Journal of Natural Sciences
  • 2021
Spironolactone’s sexual side-effects, especially in males, continue to limit the various applications of this multi-use drug.

Real-World Effectiveness of Mineralocorticoid Receptor Antagonists in Primary Aldosteronism

Despite evidence that reversal of renin suppression confers cardio-renal protection in patients with PA and LRH, renin targets are followed in very few and are achieved in under half of such patients seen in an academic setting, with possibly even lower rates in community practices.

Aldosterone synthase inhibition in humans.

  • M. AziziL. AmarJ. Ménard
  • Medicine, Biology
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2013
As the effects of LCI699 on the glucocorticoid axis limit the use of higher doses range because of the loss of selectivity for CYP11B2, this aldosterone synthase inhibitor cannot replace the MR blockade in patients with hypertension, other cardiovascular or renal disorders.



Mineralocorticoid receptors and pathophysiological roles for aldosterone in the cardiovascular system.

The 30% improvement in mortality seen in the RALES trial with the addition of low-dose spironolactone to best practice therapy in moderate to severe heart failure, similarly points to an unrecognized role for aldosterone in the pathophysiology of heart failure.

Antihypertensive actions of diuretics. Comparative study of an aldosterone antagonist and a thiazide, alone and together.

Spironolactone can be a useful substitute for a benzothiadiazine derivative in the treatment of hypertension and the administration of a combination of these diuretics, a thiazide and an aldosterone antagonist, can render hypertension more readily manageable.

Spironolactone as a Nonspecific Treatment for Primary Aldosteronism

The results suggest 1) that the antihypertensive action of spironolactone is nonspecific and largely dependent on salt and water balance and 2) that maintenance of reduced plasma volume or extracellular fluid volume (ECFV) is a basic component of the pressure response of 1°A to spironlactone therapy.

Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro.

It appears that the 9 alpha, 11 alpha-position of the steroid structure is a site of the molecule which can be modified to improve the specificity of aldosterone-antagonists not only in vitro, but also in vivo.

Assessment of the antimineralocorticoid effect of RU 28318 in healthy men with induced exogenous and endogenous hypermineralocorticism

A single dose of RU 28318 in man has an antimineralocorticoid effect identical to those produced by the identical molar dose of spironolactone, and the results show that furosemide-induced hyperaldosteronism constitutes a simple and reproducible test for assessing the antiminERALOCorticoids effect of a drug.

Evaluation of aldosterone antagonists in healthy man.

Repeated administration of a medium-potency diuretic appears to provide a clinically relevant situation in which the effect of aldosterone antagonists on potassium metabolism can be assessed.

The metabolic effects of progesterone in man.

It has been demonstrated that progesterone induces growth in the sebaceous glands of rats, and in a man with Addison's disease who was maintained with added salt, 30 mg.