Effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]-3-(1H-tetrazol -5-yl)-4H-pyrido[1,2-alpha]pyrimidin-4-one (AS-35) on the resting tonus or contractions induced by agonists, such as
leukotriene (LT) D4 and specific
antigen of isolated guinea pig tracheas or human bronchi, and the in vitro anaphylactic release of
histamine and LTs from human lung fragments were investigated and compared with the effects of
FPL 55712 and
disodium cromoglycate.
AS-35 as well as
FPL 55712 did not affect the contractions induced by
acetylcholine and
histamine of the isolated guinea pig trachea. However, the compound at relatively low concentrations obviously inhibited contractions induced by
LTD4, and the antagonistic activity was stronger than that of
FPL 55712. Treatment of the isolated human bronchus with
AS-35 tended to induce the inhibition of both LTD4- and
antigen-induced contractions and the relaxation of the resting tonus in a concentration-dependent manner. The inhibitory potency
at 10(-6) g/ml was slightly stronger than that of
FPL 55712, but this was not statistically significant. The anaphylactic release of
histamine and LTs from the lung fragments appeared to be inhibited by the treatment with
AS-35 5 min prior to the
antigen challenge. From these results, it is suggested that
AS-35 is effective against allergic
asthma through antagonism towards
peptide-LTs released anaphylactically in addition to inhibition of the chemical mediator release.