SC 25125: A potent mineralocorticoid antagonist with decreased antiandrogenic activity relative to spironolactone

G. B. Cutler, M. A. Sauer, Donald (Lynn) Loriaux

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10 Citations (Scopus)

Abstract

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 is 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 and antimeneralcorticoid 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.

Original languageEnglish (US)
Pages (from-to)144-146
Number of pages3
JournalJournal of Pharmacology and Experimental Therapeutics
Volume209
Issue number1
StatePublished - 1979
Externally publishedYes

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Mineralocorticoid Receptor Antagonists
Spironolactone
Pharmacology
Gynecomastia
Drug Receptors
Mineralocorticoid Receptors
Libido
Androgen Receptors
Erectile Dysfunction
Drug Interactions
Biological Assay

ASJC Scopus subject areas

  • Pharmacology

Cite this

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abstract = "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 is 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 and antimeneralcorticoid 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.",
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