[Effect of KC-404 on allergic reactions types I-IV]

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.