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  • Title: Immunopharmacological studies on TBX, a new antiallergic drug (3). Inhibitory effects on histamine release from lung fragments and bronchoconstriction in guinea pigs.
    Author: Yanagihara Y, Kasai H, Matsui S, Ninomiya K.
    Journal: Jpn J Pharmacol; 1989 Sep; 51(1):83-92. PubMed ID: 2478743.
    Abstract:
    The effects of 9-methyl-3-(1H-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(-7) to 10(-4) 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(-4) 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(-5) g/ml induced dose-dependent reduction in the resting tonus, which was not affected by pretreatment with propranolol. Neither the leukotriene D4-induced contraction nor the prostaglandin F2 alpha-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.
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