Immunopharmacological studies on TBX, a new antiallergic drug (3). Inhibitory effects on histamine release from lung fragments and bronchoconstriction in guinea pigs.
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.
Yanagihara
Y
Y
Clinical Research Center for Allergy, National Sagamihara Hospital, Japan.
Kasai
H
H
Matsui
S
S
Ninomiya
K
K
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D013189:SRS-A / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D006633:Histamine Antagonists; D010972:Platelet Activating Factor; D011725:Pyridines; D011744:Pyrimidinones; D013189:SRS-A; C055139:pemirolast; D015237:Dinoprost