RT Journal Article
SR Electronic
T1 SC 25152: a potent mineralocorticoid antagonist with decreased antiandrogenic activity relative to spironolactone.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 144
OP 146
VO 209
IS 1
A1 G B Cutler, Jr
A1 M A Sauer
A1 D L Loriaux
YR 1979
UL http://jpet.aspetjournals.org/content/209/1/144.abstract
AB The widely used mineralocorticoid antagonist spironolactone has antiandrogenic activity that may contribute to its side effects of decreased libido, impotence and gynecomastia. We have therefore sought a less antiandrogenic analog of spironolactone that may exhibit reduced endocrine side effects. The analog SC 25152 was chosen for pharmacological testing because of the previous observation that it has considerably reduced affinity for the androgen receptor of both man and rat but exhibits an affinity for the mineralocorticoid receptor similar to that of spironolactone. Bioassays in the rat show that SC 25152 has a 60% decrease in antiandrogenicity, and a 4-fold increase in antimineralocorticoid activity compared to spironolactone, resulting in an overall reduction of antiandrogenic activity to one-tenth that of spironolactone at doses giving equal antimineralocorticoid activity. These studies demonstrate that the antiandrogenic and antimineralocorticoid activities of spironolactone analogs can be dissociated and illustrates the utility of measurements of drug-receptor interaction to identify a compound with desired pharmacological properties.