Synthesis of Substance P Analogs and Agonistic and Antagonistic Activities.

Abstract

Fourteen analogs of substance P (SP), 6 previously synthesized by a solution method and 8 newly synthesized by a solid-phase technique, were tested for agonistic and antagonistic activities utilizing the isolated guinea pig ileum. The primary objective was to achieve effective inhibitors of SP. These analogs had agonistic activities ranging from negligible to that equivalent to SP. Six of the 14 analogs had some degree of antagonistic activity. [D-Leu8, D-Phe9]-SP is an analog which constitutes a lead to new substitutions, because it had antagonistic activity, but only negligible agonistic activity. One concept for effective antagonistic activity requires negligible or no agonistic activity.