The effects of 3-isobutyryl-2-isopropylpyrazolo [1,5-a]
pyridine (KC-404), a new
anti-allergic agent, on type I to IV
allergic reactions were investigated.
KC-404 administered orally inhibited heterologous and homologous passive cutaneous anaphylaxis (PCA) reactions in guinea pigs and homologous PCA in rats; the minimum effective doses were 50, 12.5 and 3 mg/kg, respectively. However, the inhibition of PCAs by
KC-404 was incomplete so that only 50 to 60% inhibitions were obtainable even at the highest doses used.
KC-404 had no effect on increased vascular permeability by chemical mediators other than
SRS-A and hardly affected
antigen-induced degranulation of the sensitized mesenteric mast cells in vitro. These results suggest that
KC-404 exerts its effect conceivably through inhibition of the
SRS-A-mediated component of PCA.
KC-404 had no effect on type II
allergic reaction as estimated by its failure to inhibit reversed cutaneous
anaphylaxis in rats and the Forssman systemic reaction in guinea pigs. Also, no influence on
complement activity was observed in vitro and in vivo.
KC-404 (100 approximately 200 mg/kg, p.o.) produced a marked inhibition of passive and active Arthus reactions in guinea pigs and rabbits, respectively. The
tuberculin reaction in guinea pigs was not affected by
KC-404. These results suggest that
KC-404 inhibits PCAs mediated by
IgE as well as
IgG antibodies probably through a unique mechanism of action.
KC-404 was shown to be effective also on type III
allergic reaction.