Pain and inflammation evoked in human skin by bradykinin receptor antagonists.

We showed the intrinsic effects of the bradykinin (BK) receptor antagonists, NPC 567 (D-Arg-[Hyp3,D-Phe7]BK) and NPC 349 (D-Arg-[Hyp3,Thi5,8,D-Phe-7]BK), in the skin of humans. NPC 567 and NPC 349 caused dose-dependent pain, wheal, and flare on intracutaneous injection. After bradykinin, only the pain, but not the wheal and flare reactions were dose-dependent. The intravenous application of antihistamines (dimetidinmaleate and ranitidine) had little effect on pain intensity and reduced both wheal and flare response to the antagonists but not to bradykinin. We conclude that NPC 567 and NPC 349 have pain-evoking and histamine-releasing properties in the skin of humans which may limit their therapeutic and experimental use.