Inhibitory effect of methylprednisolone suleptanate (U-67590A) on anaphylactic bronchoconstriction in guinea pigs.
Effects of U-67590A, an analogue of methylprednisolone, on antigen-induced bronchoconstriction expressed as ventilation overflow were examined in ovalbumin-sensitized guinea pigs. When administered intravenously 17-18 hr before the challenge with antigen, U-67590A at doses of 10 and 30 mg/kg caused dose-dependent inhibition of increased ventilation overflow immediately after challenge. Death due to anaphylactic shock was markedly reduced by U-67590A. At 10 mg/kg (i.v.), U-67590A given 10 min before the challenge significantly inhibited the antigen-induced increase in ventilation overflow; the greatest inhibition seen 5-6 hr prior to the challenge. Pretreatment with 10 mg/kg FPL-55712 attenuated the increase in ventilation overflow during anaphylaxic shock. It is conceivable that inhibition of the leukotriene-mediated response is involved in the glucocorticoid-induced suppression of airway obstruction in anaphylaxis, and that inhibitory action of the glucocorticoid directly acting on the airway may account for the very fast onset of action.
Nomura
Y
Y
Department of Pharmacology, Tsukuba Research Laboratories, Upjohn Pharmaceuticals Limited, Ibaraki, Japan.
Hashimoto
M
M
Hayashi
S
S
D000707:Anaphylaxis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000188:drug therapy / Q000517:prevention & control; D001982:Bronchial Diseases / Q000209:etiology / Q000517:prevention & control*; D002867:Chromones / Q000494:pharmacology; D003251:Constriction, Pathologic / Q000209:etiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010047:Ovalbumin / Q000276:immunology; D013189:SRS-A / Q000037:antagonists & inhibitors; D013997:Time Factors
D000941:Antigens; D002867:Chromones; D013189:SRS-A; C006312:FPL 55712; D010047:Ovalbumin; C052305:methylprednisolone suleptanate; D008775:Methylprednisolone