BINDING OF THE ANTIINFLAMMATORY STEROID DEFLAZACORT TO GLUCOCORTICOIDRECEPTORS IN BRAIN AND PERIPHERAL-TISSUES - IN-VIVO AND IN-VITRO STUDIES

Deflazacort (DFC) is a heterocyclic glucocorticoid with anti-inflammat ory activity but with decreased side effects. In this study, we have e valuated the capacity of DFC and other glucocorticoids to reach the ce ntral nervous system (CNS) in vivo by measuring changes of [H-3]dexame thasone (DEX) binding to glucocorticoid receptors (GR) in vitro. GR oc cupation was effected by DEX in the cerebral cortex, hippocampus, pitu itary, liver and thymus, with DFC showing a similar profile except for the cerebral cortex. In contrast, corticosterone weakly occupied GR i n the thymus, pituitary and hippocampus and methyl-prednisolone was ac tive only in peripheral tissues. Furthermore, IC50 for DEX in vitro am ounted to 15-17 nM in the hippocampus and liver, whereas IC50 for the active metabolite 21-deacetyl-DFC (21-OH-DFC) was 4 times higher. 21-O H-DFC bound to type II and was absent from type I GR, When tested in e quipotent doses based on IC50 analysis, DFC and DEX similarly induced in vivo ornithine decarboxylase activity in hippocampus and liver, alt hough body weight loss after chronic treatment was significantly less for DFC. The results show that DFC distributes on the CNS similarly to DEX, induces ornithine decarboxylase activity but presents less inten sive catabolic effects, making it suitable for use as an anti-inflamma tory steroid during chronic therapeutic regimes.