A new type of bradykinin B2 receptor antagonists: bradykinin analogs with N-alkyl amino acids at position 2

Abstract It is commonly assumed that bradykinin B 2 receptor antagonists bind to a receptor site partially different from that for agonists. Thus, it is likely that there exists more than one key modification to convert bradykinin receptor agonists into antagonists. In this respect, [L-NMePhe 2 ]-BK represents the basic structure of a new type of bradykinin B 2 receptor antagonists without any replacement at position 7. This compound inhibits both in vitro bradykinin-induced contraction of the guinea pig lung strip and in vivo bradykinin-induced bronchoconstriction. Furthermore, this analog shows analgesic activity, blocks in a dose-dependent manner the bradykinin-induced Ca 2+ release from macrophages and inhibits at a concentration of 10 −13 M the bradykinin-induced cytokine release from mononuclear cells. Combinations with structural modifications previously performed for other B 2 receptor antagonists rather reduce than enhance the potency.