Immunopharmacological studies on TBX, a new antiallergic drug. (3). Inhibitory effects on histamine release from lung fragments and bronchoconstriction in guinea pigs.
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概要
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The effects of 9-methyl-3-(lH-tetrazol-5-yl)-4H-pyrido[1, 2-a]pyrimidin-4-one potassium salt (TBX), a new antiallergic drug, on histamine release from lung fragments, experimental asthma and isolated tracheal muscle were investigated in guinea pigs. TBX (10<SUP>-7</SUP> to 10<SUP>-4</SUP> g/ml) dose-dependently inhibited antigen-induced histamine release from lung fragments of guinea pigs passively sensitized with homologous IgE serum. Antigen inhalation-induced experimental asthma in passively sensitized animals was inhibited in a dose-dependent fashion by i.v. (1 to 5 mg/kg) and p.o. (10 to 100 mg/kg) administrations of TBX. In vivo bronchoconstriction by platelet-activating factor (PAF, i.v.) was also inhibited by TBX (0.3 to 10 mg/kg, i.v.). However, high concentrations of TBX (more than 3 x 10<SUP>-4</SUP> g/ml) were needed to inhibit PAF-induced platelet aggregation in vitro. With regard to the effect on isolated tracheal muscle, TBX itself at concentrations higher than 10<SUP>-5</SUP> g/ml induced dose-dependent reduction in the resting tonus, which was not affected by pretreatment with propranolol. Neither the leukotriene D<SUB>4</SUB>-induced contraction nor the prostaglandin F<SUB>2α</SUB>-Induced one was specifically antagonized by TBX. The results obtained indicate that TBX is an antiasthmatic agent effective in inhibiting both IgE- and PAF-induced bronchoconstriction, possibly by interfering with mediator release.
- 公益社団法人 日本薬理学会の論文
著者
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Yanagihara Yukiyoshi
Clinical Research Center For Allergy And Rheumatology National Hospital Organization Sagamihara Nati
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KASAI Hiroshi
Research Laboratories, Tokyo Tanabe Pharmaceutical Co., Ltd.
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NINOMIYA Kenji
Research Laboratories, Tokyo Tanabe Pharmaceutical Co., Ltd.
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MATSUI Shizuo
Research Laboratories, Tokyo Tanabe Pharmaceutical Co., Ltd.
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