EFFECT OF A NEW DUAL NEUROKININ ANTAGONIST ON AIRWAY SMOOTH-MUSCLE IN-SITU

The effect of FK224 yl-N-[N-{3-(2-pentylphenyl)-propionyl}-L-threonyl] L-allothreonyl]-L-asparaginyl)-L-serine-v-lactone, CAS 125787-94-2) o n isometric contraction of canine tracheal smooth muscle in situ was s tudied. Contraction was induced by administration of substance P, neur okinin A, and neurokinin B intra-arterially into the tracheal circulat ion in five mongrel dogs. FK224 inhibited substance P- and neurokinin A-induced contraction in a dose-dependent manner, but it did not inhib it neurokinin B-induced contraction significantly.! These data suggest that FK224 is a dual antagonist of both neurokinin I and neurokinin 2 receptors, with a similar potency in in vivo experiments.