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  • Title: Modulation of in vitro anaphylaxis of guinea-pig isolated tracheal segments by azelastine, inhibitors of arachidonic acid metabolism and selected antiallergic drugs.
    Author: Chand N, Diamantis W, Sofia RD.
    Journal: Br J Pharmacol; 1986 Feb; 87(2):443-8. PubMed ID: 3082402.
    Abstract:
    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.
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