title: Effects of the new antiallergic drug 11-oxo-11H-pyrido[2,1-b] quinazoline-2-carboxylic acid on immediate allergic reactions.
abstract: The effects of 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857) on immediate type, particularly type I allergic reactions were investigated and the following results were obtained. 48-h homologous passive cutaneous anaphylaxis (PCA) in rats was inhibited by oral administration of Sm 857 from the 4th h to the 30th min before antigen challenge and by intravenous administration from the 2nd h to just before antigen challenge. 48-h homologous PCA in rats was inhibited dose-dependently by oral administration of Sm 857 at 1-50 mg/kg 30 min before antigen challenge. On the other hand, the intravenous administration 10 min before antigen challenge showed similar dose-dependent effects on PCA and the effects were significant at doses of 0.5-2 mg/kg. The oral administration of Sm 857 for 1-4 weeks reduced the PCA inhibitory effect in comparison with single administration. Sm 857 injected intravenously twice at intervals of 15-120 min showed no change in inhibitory effect. The PCA inhibitory effect of Sm 857 in adrenalectomized rats was reduced markedly when compared with that in sham-operated rats. On the other hand, adrenalectomy had no influence on the inhibitory effect of tranilast. Sm 857, tranilast and ketotifen inhibited histamin-induced capillary permeability in rats and, in particular, the effect of ketotifen was conspicuous. Sm 857, tranilast and ketotifen significantly inhibited antigen-induced histamine release from the peritoneal cavity of passively sensitized rats. Release of slow reacting substance of anaphylaxis (SRS-A), on the other hand, was inhibited significantly by Sm 857 and ketotifen. Sm 857 showed a tendency to inhibit antigen-induced histamine release from the lung tissue of passively sensitized guinea pigs and significantly inhibited SRS-A release. Sm 857 inhibited histamine- and leukotriene D4 (LTD4)-induced contraction in the lung parenchyma and the tracheal muscle. However, the drug had no effect on contraction of the ileum. Sm 857 showed a tendency to inhibit the Schultz-Dale reaction in the lung parenchyma ana the ileum. Both oral and intravenous administration of Sm 857 showed an inhibitory effect on experimental asthma in guinea pigs, which was similar to that of tranilast.
mesh_terms: D000818:Animals; D001249:Asthma / Q000517:prevention & control; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D006969:Hypersensitivity, Immediate / Q000188:drug therapy*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism / Q000494:pharmacology; D012882:Skin Tests; D013618:Tachyphylaxis
chemical_list: D011799:Quinazolines; D013189:SRS-A; C051309:doqualast