A new generation of bradykinin antagonists

Abstract Bradykinin B 2 receptors are constitutively expressed, and require the entire peptide chain of bradykinin for recognition. Expression of B 1 receptors is induced in inflammation; they recognize BK-(1–8). Heretofore blockade of all the actions of bradykinin required two different antagonists, one for each class of receptors. The new antagonists described here are full chain antagonists having high potency on B 2 receptors, but they are also very potent antagonists for B 1 receptors. They are highly resistant to kininases and show very long action in vivo. These antagonists contain the novel amino acid α-(2-indanyl)glycine (Igl) at positions 5 and 7. The peptide DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg (designated B9430) shows all these desirable characteristics. It represents a new class of bradykinin antagonist peptides.