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.