Prorenone

Prorenone (SC 23133) is a spironolactone-type steroidal mineralocorticoid receptor (MR) antagonist that can cross the blood-brain barrier, with low affinity for glucocorticoid receptors and rat prostate androgen receptors. Prorenone inhibits the binding and action of Aldosterone (HY-113313), blocks its induced nuclear receptor activity and stimulated sodium transport, antagonizes aldosterone-induced urinary potassium excretion, and prevents aldosterone-induced elevation of blood pressure. Prorenone can be used in research related to hypertension^[1][2]. In Vitro:Prorenone exhibits slightly higher binding affinity for renal mineralocorticoid receptors than aldosterone in vitro, and shows higher specificity for mineralocorticoid receptors over glucocorticoid receptors and androgen receptors compared with Spironolactone (HY-B0561)^[1].
Prorenone binds to a single class of specific sites with high affinity and low capacity in soluble renal proteins from the kidneys of adrenalectomized male Wistar rats, with a mean dissociation constant (K_d) of 1.54 nM^[2].
Prorenone (1-10 nM; 20-60 min) forms cytosolic complexes with renal receptors in kidney homogenates from adrenalectomized male Wistar rats, but these complexes do not translocate to the nucleus, and exert an equivalent inhibitory effect on both cytosolic and nuclear binding of aldosterone^[2]. In Vivo:Prorenone (0.005-0.02 μg/h; intracerebroventricularly; continuous infusion; 30 days) blocks the aldosterone-induced elevation of systolic blood pressure in unilaterally nephrectomized rats, with no significant effects on urine volume, body weight, or organ weight ratios when administered alone or with aldosterone^[1].
Prorenone (1.5 mg; i.p.; single dose) significantly antagonizes aldosterone-induced kaliuresis in adrenalectomized rats^[2].