Modulation of in vitro anaphylaxis of guinea‐pig isolated tracheal segments by azelastine, inhibitors of arachidonic acid metabolism and selected antiallergic drugs

Abstract

1 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. 2 Indomethacin produced a significant leftward shift of the antigen concentration-effect curve. 3 The inhibitory activity ofazelastine on anaphylactic responses in guinea-pig trachea was dependent on the duration of exposure (preincubation period). 4 The relative order ofpotency (antianaphylactic activity) at calculated IC50 level was as follows: FPL 55712 (a leukotriene receptor antagonist) > nordihydroguaiaretic acid (a lipoxygenase inhibitor) > pbromophenacyl bromide (a phospholipase A2 inhibitor) > BW 755c (a dual inhibitor of lipoxygenase and cyclo-oxygenase) > theophylline (a phosphodiesterase inhibitor) > azelastine > diphenhydramine (HI histamine-receptor antagonist) > ketotifen > disodium cromoglycate. FPL 55712 (added 5 min before antigen challenge) was about 12 times as potent as azelastine (added 2 h before antigen challenge). 5 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 ofthe products oflipoxygenase/leukotriene synthetase pathway (e.g., leukotrienes) in the mediation of allergic responses in airway smooth muscles.

Effects of Antiasthma Drugs on Superoxide Anion Generation from Human Polymorphonuclear Leukocytes or Hypoxanthine-Xanthine Oxidase System

“…Antiallergic drugs have been demonstrated to in hibit the release of histamine from mast cells and ba sophils [33,34], to block smooth muscle contraction to various spasmogens [35], and to relax airway smooth muscle [15]. We found that azelastine inhibited O3 generation in PMNs from asthmatic patients in a dose-dependent fashion.…”

Effect of NZ-107, a Newly Synthesized Pyridazinone Derivative, on Antigen-Induced Contraction of Human Bronchial Strips and Histamine Release from Human Lung Fragments or Leukocytes

“…Such constrictions are caused by many bronchoactive substances released from mast cells [15][16][17]. In the present study, we reported the effects of NZ-107, amlexanox, DSCG and salbutamol on the anti gen-induced contraction of isolated human tracheal mus cle passively sensitized with atopic serum.…”

“…Since some investigators have reported that an leukotriene receptor antagonist (FPL-55712) and a lipoxygenase inhibitor (NDGA) inhibited the antigen-induced contrac tion of isolated guinea pig tracheal muscle [16,21,22], lipoxygenase products, especially leukotrienes, are con sidered to play an important role in the antigen-induced contraction of tracheal muscle. Regarding the effects of NZ-107, Yamamoto et al [2] reported that NZ-107 inhib ited the antigen-induced contraction of isolated guinea pig tracheal muscle by inhibiting SRS-A release and its re sponses.…”

Synthesis of 9-Aryl-3-methyl-1,8-dioxo-2,10-dioxanthens

“…此 外, 苯并吡喃及其衍生物还广泛应用于抗发育不良 [2] 、 抗过敏 [3] 、抗菌、抗癌 [4,5] 、抗过敏性气管炎 [6] 及治疗糖 尿病 [7] 等方面. 氧杂蒽为含有苯并吡喃结构单元的化合 物, 其良好的生物活性(如抗痉挛和调节植物生长等 [8] )…”