Glucocorticoid/antiinflammatory activities of nonsteroidal phenylpyrazoles in the rat.
Six nonsteroidal phenylpyrazoles are described that have significant glucocorticoid and antiinflammatory activities. These agents competed with dexamethasone for the glucocorticoid receptor from the rat thymus, suppressed adrenal weight when administered orally to intact female rats, produced liver glycogen deposition and thymolysis when administered orally to adrenalectomized male rats, and reduced cotton granuloma formation when administered in the cotton pellet. In addition, in the latter model, no systemic activity (thymolysis or reduced body weight gain) was seen with doses up to 500 to 5000 times the dose which reduced granuloma formation. At least one compound was more potent than methylprednisolone in three of the four rat assay systems used. The compounds described are structurally different from conventional steroidal glucocorticoids but possessed potent glucocorticoid activities. However, they exhibited antiinflammatory activity without evidence of systemic activity when administered locally.
D000284:Administration, Oral; D000287:Administration, Topical; D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents; D001667:Binding, Competitive; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids; D066298:In Vitro Techniques; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D008112:Liver Glycogen; D011720:Pyrazoles; D011965:Receptors, Glucocorticoid