Modulation of in vitro anaphylaxis of guinea-pig isolated tracheal segments by azelastine, inhibitors of arachidonic acid metabolism and selected antiallergic drugs.
The ability of azelastine to influence antigen-induced contractile responses (Schultz-Dale phenomenon) in isolated tracheal segments of the guinea-pig was investigated and compared with selected antiallergic drugs and inhibitors of arachidonic acid metabolism. Indomethacin produced a significant leftward shift of the antigen concentration-effect curve. The inhibitory activity of azelastine on anaphylactic responses in guinea-pig trachea was dependent on the duration of exposure (preincubation period). The relative order of potency (antianaphylactic activity) at calculated IC50 level was as follows: FPL 55712 (a leukotriene receptor antagonist) greater than nordihydroguaiaretic acid (a lipoxygenase inhibitor) greater than p-bromophenacyl bromide (a phospholipase A2 inhibitor) greater than BW 755c (a dual inhibitor of lipoxygenase and cyclo-oxygenase) greater than theophylline (a phosphodiesterase inhibitor) greater than azelastine greater than diphenhydramine (H1 histamine-receptor antagonist) greater than ketotifen greater than disodium cromoglycate. FPL 55712 (added 5 min before antigen challenge) was about 12 times as potent as azelastine (added 2 h before antigen challenge). The incubation of tracheal segments with azelastine and BW 755c for a period of 30 min was found to inhibit indomethacin-augmented anaphylactic responses. These observations seem to suggest that azelastine and BW 755c interfere with the synthesis/release of the products of lipoxygenase/leukotriene synthetase pathway (e.g., leukotrienes) in the mediation of allergic responses in airway smooth muscles.
Chand
N
N
Diamantis
W
W
Sofia
R D
RD
D000403:Airway Resistance / Q000187:drug effects*; D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D000941:Antigens / Q000276:immunology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis*; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000188:drug therapy*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D000941:Antigens; D001095:Arachidonic Acids; D010793:Phthalazines; D011724:Pyridazines; D016718:Arachidonic Acid; D007213:Indomethacin; C020976:azelastine