The
antiallergic activity profile of
RHC 3414 (7-phenylpyrido (3', 2': 4, 5)-thieno (3.2-d)-1, 2, 3-
triazine-4(3H)-one) has been compared with that of
disodium cromoglycate (DSCG) in several in vitro and in vivo models of
anaphylaxis and
inflammation.
RHC 3414 was approximately 50 times more potent than DSCG as an inhibitor of
antigen-induced release of
histamine (AIR) from rat mast cells (RMC) in vitro. As an inhibitor of mediator release, the activity profile of
RHC 3414 was identical to that of DSCG in the following respects: inhibition of
IgE-mediated release of
histamine from RMC but not human basophils (HUB), rapid loss of inhibitory activity as a function of time prior to
antigen challenge, inability to inhibit the release of
histamine from RMC stimulated by non-immunologic
secretagogues as well as IgG1-mediated histamine release from guinea-pig lung slices. In vivo, given orally the
sodium salt of
RHC 3414 (RHC 3414-Z) was a potent inhibitor of passive cutaneous anaphylaxis (PCA) in the rat. Administered intraperitoneally, RHC 3414-Z was approximately 30 times as potent as DSCG as an inhibitor of
IgE-mediated PCA in the rat without any antihistaminic or antiserotonin activity. RHC 3414-Z also inhibited adjuvant-induced inflammatory responses in the rat but had no effect on
carrageenan-induced
edema formation in vivo or on
phospholipase A2 or
cyclooxygenase activity in vitro. We conclude that
RHC 3414 is a potent
antiallergic agent with a mechanism of action similar to that of DSCG. In addition,
RHC 3414 may possess the ability to inhibit chronic inflammatory processes, an attribute which should prove useful in the prophylactic treatment of
asthma.