Epleremone

Epleremone

Recent studies with eplerenone, a novel selective aldosterone receptor antagonist.[Pubmed:11714095]

Curr Opin Pharmacol. 2001 Apr;1(2):190-6.

Activation of the renin-angiotensin-aldosterone system is associated with unsatisfactory outcomes in patients with hypertension and congestive heart failure, in that activation of this system is correlated strongly with both the incidence and extent of end-organ damage. Despite the availability of the angiotensin-converting enzyme inhibitors and the AT1 receptor antagonists, unblocked aldosterone levels remain an important risk factor for cardiovascular disease progression. New preclinical data generated over the past few years strongly support the hypothesis that aldosterone has important deleterious effects on the cardiovascular system independent of the classical action of this hormone on renal epithelial cells. The new selective aldosterone receptor antagonist eplerenone has been shown to produce significant cardioprotective effects in experimental models of cardiovascular disease. Early clinical testing suggests that eplerenone may have important therapeutic benefit in the treatment of hypertension and heart failure.

Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro.[Pubmed:2949071]

J Pharmacol Exp Ther. 1987 Feb;240(2):650-6.

The use of spironolactone, the most commonly used antimineralocorticoid compound, is limited by the occurrence of sexual endocrine effects. New antagonists are therefore required which lack these unwanted effects. Three 9 alpha,11 alpha-epoxy-derivatives of known aldosterone antagonists (spironolactone, prorenone and mexrenone) have been characterised in vitro and in vivo. In each experiment spironolactone was run as a reference. The introduction of the epoxy-group only marginally affected the binding affinity of these compounds for the mineralocorticoid receptor, whereas it caused a decrease for the androgen and progesterone receptors of between 10- and 500-fold. In vivo, all three epoxy-derivatives (3 mg/kg) were potent aldosterone antagonists, 1 to 2 times the potency of spironolactone in the rat. Parallel to the decreased affinity for the androgen and progesterone receptor in vitro, there was a 3- to 10-fold decrease of the antiandrogenic and progestagenic effect compared to spironolactone in the rat and in the rabbit, respectively. Virtually no disturbance of the vaginal or ovulatory cycle was observed with either epoxymexrenone or epoxyprorenone, although epoxyspironolactone caused a 20% decrease in ovulation. It appears therefore 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.