Antagonists of Substance P from Emphasis on Position 11.

Abstract
Ten analogs of substance P (SP) were designed and synthesized. The agonist and antagonist activities against SP were assayed on the isolated guinea pig ileum. The prime designs were changes of the important Met11 to include Leu11, Thr11, D-Leu11 and D-Ala11. Step-wise designs of changing D-Arg1 and D-Pro2 to the corresponding L-configurations resulted in decreasing antagonist activity. Changing Leu11 to D-Leu11 and D-Ala11 reduced antagonist activity. [D-Arg1, D-Pro2, D-Trp7, D-Trp9, Leu11]-SP is the most potent antagonist of this group of analogs and required a 100-fold increase in the concentration of SP to give 50% of the maximal response caused by SP.