[Effects of KC-404 on bronchial anaphylactic reactions]

The effects of 3-isobutyryl-2-isopropylpyrazolo [1,5-a] pyridine (KC-404), a new anti-allergic agent with a unique mode of action, on bronchial anaphylactic reactions were investigated in guinea pigs and rats. The inhibitory effects of orally administered KC-404 on systemic anaphylactic reaction caused by intravenous antigen and on anaphylactic bronchoconstriction caused by inhaled antigen in guinea pigs actively sensitized with egg albumin were observed at doses of 100 mg/kg and 10 mg/kg, respectively. When these animals were pretreated with diphenhydramine and atropine before antigen challenge, the inhibitory effects of KC-404 were markedly enhanced; doses as low as 0.25 to 0.5 mg/kg p.o. were effective in this situation. In guinea pigs similarly sensitized as above, KC-404 injected i.v. after the maximum development of antigen-induced constriction of airways resulted in a rapid dilatation. KC-404 was about 100 times as potent as aminophylline in this respect. KC-404 inhibited passive anaphylactic bronchoconstriction in rats mediated by an IgE antibody at an oral dose of 2.5 mg/kg. The inhibitory effect of KC-404 (10 mg/kg) persisted for at least 6 hr. These results indicate that KC-404 is orally effective in inhibiting anaphylactic bronchoconstrictions mediated by IgE as well as IgG antibodies. Furthermore, KC-404 is suggested to be able to control the SRS-A-induced component of bronchospasm.