The inhibitory effect of 3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]
pyridine (KC-404) on aerosolized
methacholine- and
histamine-induced increase in total respiratory resistance (Rrs) was determined in monkeys using the forced 3 Hz oscillation method and was compared with the effect of
aminophylline. The effects of several derivatives of
KC-404 on
methacholine-induced bronchoconstriction were also determined. All of the i.v. administered
pyrazolopyridine derivatives showed an inhibition of the increase in Rrs induced by aerosolized
methacholine. Among these derivatives,
KC-404 exerted the most potent bronchodilating effect.
KC-404 also inhibited the
histamine-induced increase in Rrs. These effects of
KC-404 were more potent than those of
aminophylline. On the other hand, the dose of
KC-404 tested caused an increase in heart rate, although the degree was moderate as compared with
aminophylline. From the results obtained in this study, it is considered that the
pyrazolopyridine derivatives, particularly
KC-404, may be promising
bronchodilators for the treatment of
bronchial asthma.