ANTIPROGESTINS AND IATROGENIC GLUCOCORTICOID RESISTANCE

The antiglucocorticoid action of the antiprogestin RU 38486 has interf ered with its successful clinical application in long-term treatment. Several new antiprogestins (Org 31710, Org 31806 and ZK 98299) have re cently been developed with the aim to eliminate this side-effect. We h ave used a human lymphocyte proliferation assay to estimate the antigl ucocorticoid potency of RU 38486 and the newer antiprogestins. In this assay 100 nmol/L RU 38486 shifted the dexamethasone inhibition curve by at least one order of magnitude. The other antiprogestins showed no effect at 100 nmol/L. RU 38486 (30 nmol/L) was able to antagonize 100 0 nmol/L dexamethasone. The other antiprogestins showed only slight ef fects even at 1000 nmol/L. We conclude that the new antiprogestins hav e antiglucocorticoid effects that are one to two orders of magnitude l ower than that of RU 38486. This may make them more suitable than RU 3 8486 for application in long-term antiprogestin treatment.