The effect of a TXA2 receptor antagonist ON-579 on experimental allergic reactions.
The effect of a thromboxane A2 (TXA2) receptor antagonist, ON-579, on experimental allergic skin and airway reactions was studied in vivo. ON-579 at doses of 1 and 20 mg/kg clearly inhibited U-46619-induced increases in respiratory resistance (Rrs) in guinea pigs. ON-579 at doses of 1, 20 and 50 mg/kg inhibited the aerosolized antigen-induced biphasic increase in Rrs in guinea pigs. Moreover, ON-579 clearly inhibited repeated aeroantigen-induced airway hyperreactivity in guinea pigs. ON-579, however, did not have any significant effects on allergic cutaneous reactions in rats. These results suggest that ON-579 is a relatively selective TXA2 antagonist, especially in the airways, and indicate the efficacy of ON-579 on antigen-induced increase in airway resistance and antigen-induced airway hyperreactivity in guinea pigs.
D000336:Aerosols; D000403:Airway Resistance; D000818:Animals; D000941:Antigens / Q000276:immunology; D001183:Arthus Reaction / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003208:Concanavalin A / Q000494:pharmacology; D004140:Dinitrophenols / Q000276:immunology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006967:Hypersensitivity / Q000517:prevention & control*; D007665:Ketotifen / Q000494:pharmacology; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis; D010642:Phenoxyacetates / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012140:Respiratory Tract Diseases / Q000276:immunology / Q000517:prevention & control; D012710:Serum Albumin, Bovine / Q000276:immunology; D012871:Skin Diseases / Q000276:immunology / Q000517:prevention & control; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
D000336:Aerosols; D000941:Antigens; D004140:Dinitrophenols; D010642:Phenoxyacetates; D017482:Receptors, Thromboxane; D013449:Sulfonamides; C034638:dinitrophenyl-bovine serum albumin; D003208:Concanavalin A; C096827:ON 579; D012710:Serum Albumin, Bovine; D006632:Histamine; D010047:Ovalbumin; D007665:Ketotifen