Suda H, Nagai H, Miura T, Iwama T, Koda A
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1992 Sep;47(1):41-9. doi: 10.1016/0952-3278(92)90184-k.
The effects of 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone (NZ-107) on immediate type hypersensitivity reactions in rats and guinea-pigs were studied. 1. When NZ-107, at a dose of 50 mg/kg (i.p.) or 100 mg/kg (orally), was administered to rats, 48-h homologous passive cutaneous anaphylaxis (PCA) reaction and histamine-, leukotriene C4 (LTC4)- and leukotriene D4 (LTD4)-induced skin reactions were suppressed by the agent. 2. NZ-107 (10(-6) g/ml) inhibited both LTC4- and LTD4-induced contractions of isolated rat stomach smooth muscle. 3. NZ-107 inhibited antigen-induced histamine release from rat peritoneal mast cells by 26% at a concentration of 10(-4) g/ml. 4. NZ-107, at doses of 25 and 50 mg/kg (orally), significantly inhibited guinea-pig 3-h heterologous PCA reaction. 5. NZ-107 inhibited antigen-induced histamine release from guinea-pig lung tissue by 17% and 48% at concentrations of 5 x 10(-5) and 10(-4) g/ml, respectively. 6. NZ-107, at doses of 25 and 50 mg/kg (i.p.), inhibited antigen-induced bronchoconstriction and eosinophil accumulation in the bronchoalveolar lavage fluid (BALF) of guinea-pigs. These results suggest that NZ-107 has anti-allergic action including inhibition of eosinophil accumulation in an antigen-challenged airway lesion in rats and guinea-pigs. The anti-allergic action of this agent is thought to be due to its action as a histamine and LT antagonist and its consequent inhibition of antigen-induced histamine release.
研究了4-溴-5-(3-乙氧基-4-甲氧基苄基氨基)-3(2H)-哒嗪酮(NZ-107)对大鼠和豚鼠速发型超敏反应的影响。1. 当以50mg/kg(腹腔注射)或100mg/kg(口服)的剂量给大鼠施用NZ-107时，该药物可抑制48小时同源被动皮肤过敏反应(PCA)以及组胺、白三烯C4(LTC4)和白三烯D4(LTD4)诱导的皮肤反应。2. NZ-107(10(-6)g/ml)抑制LTC4和LTD4诱导的离体大鼠胃平滑肌收缩。3. NZ-107在浓度为10(-4)g/ml时可抑制抗原诱导的大鼠腹腔肥大细胞组胺释放26%。4. 以25和50mg/kg(口服)的剂量，NZ-107可显著抑制豚鼠3小时异源PCA反应。5. NZ-107在浓度分别为5×10(-5)和10(-4)g/ml时，可分别抑制抗原诱导的豚鼠肺组织组胺释放17%和48%。6. 以25和50mg/kg(腹腔注射)的剂量，NZ-107可抑制抗原诱导的豚鼠支气管收缩以及支气管肺泡灌洗液(BALF)中嗜酸性粒细胞的聚集。这些结果表明，NZ-107具有抗过敏作用，包括抑制大鼠和豚鼠抗原激发气道病变中嗜酸性粒细胞的聚集。该药物的抗过敏作用被认为是由于其作为组胺和白三烯拮抗剂的作用以及随后对抗原诱导的组胺释放的抑制。
