Orally active mineralocorticoid agonists and antagonists: delta 1-derivatives of aldosterone and 18-deoxyaldosterone.
The effect of delta 1 unsaturation on the oral effectiveness of a representative mineralocorticoid agonist and antagonist was investigated in an adrenalectomized rat bioassay. Dehydrogenation at the 1.2 position did not alter the qualitative nature of the mineralocorticoid activity of the parent compound. Thus delta 1-aldosterone (21,18-dihydroxy-11 beta, 18-oxido-1,4-pregnadiene-3,20-dione) retained pure mineralocorticoid agonism, and delta 1-18-deoxyaldosterone (21-hydroxy-11 beta, 18-oxido-1,4-pregnadiene-3,20-dione)demonstrated the same relative degree of predominant antagonism as 18-deoxyaldosterone (21-hydroxy-11 beta, 18-oxido-4-=pregnene-3,20-dione) itself. In each instance, receptor affinity was diminished by 1,2 unsaturation, but this effect was offset by the greater bioavailability of the delta 1 derivatives on oral administration. (Endocrinology 108: 517, 1981)
D000284:Administration, Oral; D000309:Adrenal Insufficiency / Q000188:drug therapy*; D000450:Aldosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D001682:Biological Availability; D004353:Drug Evaluation, Preclinical; D007668:Kidney / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism
D000451:Mineralocorticoid Receptor Antagonists; D011956:Receptors, Cell Surface; C020274:18-deoxyaldosterone; D000450:Aldosterone