In rats, roxibolone counteracts the catabolic effects (control of nitrogen balance) and increased alkaline phosphatase levels induced by the potent glucocorticoid dexamethasone phosphate. It does not bind to the glucocorticoid receptor however, and its antiglucocorticoid activity may instead be mediated by enzyme inhibition. In accordance, 11α- and 11β-hydroxyprogesterone are known to be potent inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD), which is responsible for the biosynthesis of the potent endogenous glucocorticoids cortisol and corticosterone (from the precursors deoxycortisol and deoxycorticosterone, respectively). As roxibolone is 11β-hydroxylated similarly, it may act in a likewise fashion. However, formebolone was found to be a very weak inhibitor of 11β-HSD type 2, although this specific isoenzyme is responsible for the inactivation of glucocorticoids rather than their production.
