Binding of ester and amide epimers of 20 zeta-dihydroprednisolonic acid to cytosol receptors and their acute pharmacological activities in rats.

The competitive binding of two new classes of anti-inflammatory steroids, the esters and amides derived from the epimers of 20 zeta-dihydroprednisolonic acid, to cytosol receptors from rat liver and thymus was studied. The relative inhibition of [3H]dexamethasone binding by the steroid derivatives was the same, irrespective of the receptor source, with the following order: dexamethasone greater than prednisolone greater than methyl 17,20 alpha-acetonidodihydroprednisolonate greater than methyl 17,20 beta-acetonidodihydroprednisolonate greater than N-propyl 20 alpha-dihydroprednisolonamide greater than methyl 20 alpha-dihydroprednisolonate greater than methyl 20 beta-dihydroprednisolonate greater than N-propyl 20 beta-dihydroprednisolonamide. The alpha-epimer of the steroids always showed a higher binding affinity than the corresponding beta-epimer. In an acute pharmacological study, prednisolone induced the suppression of plasma corticosterone and an increase in tyrosine aminotransferase activity and glycogen content of rat liver. The esters and amides had no effect on these parameters except in the case of the acetonide derivatives of the steroid acid esters which slightly increased liver glycogen content.