Aldosterone Antagonism by 17-Spirolactosteroids

Quantitative comparison of aldosterone antagonists in normal human subjects: prediction of therapeutic potency.

“…However, another steroidal aldosterone antagonist, SC8109, was extensively studied in patients (Liddle, 1958;Slater, 1960;Gantt, 1961;Drill, 1962). SC8109 (17-hydroxy-3-oxo-19-nor-17a-pregn-4-ene-21 car-boxylic acid, y lactone) structurally resembles spironolactone ( Figure 1) which has found use in the treatment of oedematous states and essential hypertension (Ochs et al, 1978).…”

The Hormonal Control of Body Sodium

“…One such, a 17-spirolactosteroid now marketed as spironolactone, was synthesised by Kagawa, Cella and Van Arman (1957) who were able to show in rats that the compound, whose chemical structure was designed to resemble that of aldosterone and so inhibit its action competitively, was biologically inert unless the adrenal glands were present. In dog and man the pharmacological properties of spironolactone in doses which are too low to have any physiological or toxic effect are, convincingly, only those of a mineralocorticoid antagonist at the renal tubular level (Liddle, 1958;Slater, 1960). Ross and Winternitz (1961) have shown that, in a single subject takiing spironolactone, sodium deprivation modifies the renal response so that after five days on a rice diet containing only 3 mEq of sodium, equilibration with intake had still not been reached; furthermore, the rate of fall of urinary sodium excretion (half-time 1.45 days) was significantly slower than the rate of fall observed in normal subjects (mean half-time 0.54 days SD 0.12 days).…”

“…In cardiac failure the effect of aldosterone antagonism is small (Bartter, Gann and Thomas, 1960) unless cardiac cirrhosis of the liver has supervened (Slater, 1960) but then, haemodynamic factors predominating, hyperaldosteronism is usually not a conspicuous feature of cardiac failure in contrast to the intense hypersecretion of aldosterone in patients with the nephrotic syndrome or cirrhosis of the liver. But, if inappropriate overproduction of aldosterone is really important in cedema formation, prolonged administration of aldosterone or other mineralocorticoid steroid hormones such as desoxycorticosterone might be expected to lead to sodium retention and ultimately the appearance of cedema.…”