Effects of the new antiallergic drug 11-oxo-11H-pyrido[2,1-b] quinazoline-2-carboxylic acid on type I allergic reactions.

Antiallergic effects of the newly synthesized, quinazoline derivative 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857) were investigated. The following results were obtained. 1. Anaphylactic and non-immunologic histamine and slow reacting substance of anaphylaxis (SRS-A) release from guinea pig lung fragments was dose-dependently inhibited by 10(-6)-10(-4) and 10(-7) -10(-4) g/ml of Sm 857, respectively. Similar inhibition of the mediator release by the compound was obtained from the experiments of passively sensitized monkey and human lung fragments by antigen. 2. Seven-day passive cutaneous anaphylaxis of guinea pigs was not inhibited at 1-20 mg/kg (i.v.) of Sm 857, but inhibited at 20-100 mg/kg (p.o.) in some experiments without dose dependency. 3. Cutaneous anaphylaxis and histamine-induced cutaneous reaction in guinea pigs were hardly affected by the treatment of 50 and 100 mg/kg (p.o.) of Sm 857. 4. Passive systemic anaphylaxis in guinea pigs was not inhibited at 50-200 mg/kg (p.o.) of Sm 857. 5. Arthus reaction in rabbits was slightly and dose-dependently enhanced at 50-200 mg/kg given twice p.o. 6. Sm 857 (10(-6)-10(-4) g/ml) exhibited antispasmogenic activity against histamine and leukotriene D4 in isolated human bronchi and guinea pig trachea, however, this activity is attributable to non-specific musculotropic smooth muscle relaxation. From these results it may be concluded that Sm 857 exerts preferential effect on the respiratory system and that it might be useful in allergic asthma.