Synthesis and biological activities of substance P antagonists.
Several substance P analogues containing various D-amino acid modifications have been synthesized by the solid-phase procedure, detached from the solid support by ammonolysis, and purified by gel filtration combined with reversed-phase chromatography. Three compounds were fair to very potent competitive antagonists of substance P on three bioassays, i.e., guinea pig ileum, rabbit mesenteric vein, and guinea pig trachea. [Arg6,D-Trp10]SP(6-11) is a reasonable antagonist in all three bioassays and [D-Pro4,D-Trp7,9]SP(4-11) is a very potent competitive antagonist with pA2 values ranging around 6.0.
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008642:Mesenteric Veins / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011817:Rabbits; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D013373:Substance P