Ws9326a, a novel tachykinin antagonist isolated from streptomyces violaceusniger no. 9326: II. Biological and pharmacological properties of ws9326a and tetrahydro-ws9326a (fk224)

Abstract

WS9326A binds competitively to [3H]substance P (NK-1 receptor) binding sites on guinea-pig lung membranes (IC50 = 3.6× 10-6m), and acts as a tachykinin antagonist in various functional assays. WS9326A inhibited tracheal constrictions produced by exogenously added substance P and neurokinin A, with IC50 values of 9.7 × 10-6m and 3.5 × 10-6m, respectively. WS9326A inhibited neurokinin A-induced bronchoconstriction in a dose dependent manner when administered to guinea-pigs intravenously together with neurokinin A, and was also effective in preventing capsaicin-induced bronchoconstriction, which is known to be caused by release of endogenous tachykinins (substance P and neurokinin A). FK224 (tetrahydro-WS9326A; catalytic hydrogenation of WS9326A gave FK224) was more potent than WS9326A in the [3H]substance P receptor binding assay using guinea-pig lung membrane (IC50= 1.0 × 10-7 m). © 1992, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.