Acute effects of deflazacort and its metabolite 21-desacetyl-deflazacort on allergic reactions.
The acute effects of deflazacort (MDL 458, CAS 14484-47-0) and its metabolite, 21-desacetyl-deflazacort, on allergic reactions in animal models were investigated and compared with those of prednisolone. Deflazacort, 21-desacetyl-deflazacort and prednisolone all inhibited 48-h homologous passive cutaneous anaphylaxis in rats, but had no significant effects on active systemic anaphylaxis in mice, on the Schultz-Dale reaction in the isolated guinea-pig trachea or on compound 48/80-induced histamine release in rat peritoneal mast cells. All three agents inhibited reversed cutaneous anaphylaxis in rats and the Arthus reaction in mice. The inhibitory effects of deflazacort on the passive cutaneous anaphylaxis, the reversed cutaneous anaphylaxis and the Arthus reaction were similar to those of 21-desacetyl-deflazacort and were stronger than those of prednisolone. Delayed type hypersensitivity in mice was also inhibited by deflazacort and 21-desacetyl-deflazacort, but prednisolone, at the doses used in the present study, had little effect on this immune response. These findings indicate that while deflazacort and 21-desacetyl-deflazacort have stronger anti-allergic effects than prednisolone, they seem to have little acute effect on mast cell degranulation or on chemical mediators at the receptor site.
Omote
M
M
Marion Merrell Dow, Osaka, Japan.
Sakai
K
K
Mizusawa
H
H
D000707:Anaphylaxis / Q000188:drug therapy; D000818:Animals; D001183:Arthus Reaction / Q000188:drug therapy; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy*; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009130:Muscle, Smooth / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011239:Prednisolone / Q000627:therapeutic use; D011282:Pregnenediones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D007166:Immunosuppressive Agents; D011282:Pregnenediones; C048465:21-deacetyldeflazacort; D011239:Prednisolone; C021988:deflazacort