Pharmacological characterization of a substance P antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P.

The substance P antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P produced parallel log dose-response curve shifts to both substance P and eledoisin on five in vitro smooth muscle preparations. The slope values of Arunlakshana-Schild plots were not significantly different from unity suggesting that it acts as a simple competitive antagonist on all five preparations with an association constant (Ka) in the range of 0.3-1.5 X 10(6)M-1. The Ka value of the antagonist was always slightly greater when tested against eledoisin than against substance P; however, this difference appears too small to suggest that these two agonists are acting on different receptor sub-types.