A COMPETITIVE KININ RECEPTOR ANTAGONIST, [DARG0, HYP3, DPHE7]-BRADYKININ, DOES NOT AFFECT THE RESPONSE TO NASAL PROVOCATION WITH BRADYKININ

1 In two double-blind, placebo controlled studies, we tested the effects of intransal administration of 500-mu-g of a competitive kinin receptor antagonist, [DArg0, Hyp3, DPhe7]-bradykinin (NPC 567), on the response to nasal provocation with 20-mu-g of bradykinin. Nasal lavage was performed before and after provocation, and subjects recorded symptom scores. Lavages were assayed for albumin and TAME-esterase activity (indicators of vascular permeability). 2 In our initial study, 12 subjects received NPC 567 or placebo 5 min before bradykinin. After placebo, bradykinin challenge resulted in values (mean +/- s.e. mean) for albumin, TAME-esterase activity and total symptom scores of 275 +/- 51-mu-g ml-1, 32.1 +/- 7.2 counts min-1 x 10(-3), and 1.8 +/- 0.5, respectively. After NPC 567, bradykinin challenge resulted in values of 317 +/- 99-mu-g ml-1, 31.4 +/- 6.9 counts min-1 x 10(-3), and 2.6 +/- 0.4 for these parameters. No significant difference was observed between placebo and drug treatment for any parameter. 3 To evaluate if the lack of drug effect was due to its enzymatic degradation prior to bradykinin administration, a second study was performed in which NPC 567 was coadministered with bradykinin (n = 8). After placebo-bradykinin challenge, values of 168 +/- 42-mu-g ml-1, 11.3 +/- 4.0 counts min-1 x 10(-3), and 2.8 +/- 0.6 were recorded for albumin, TAME-esterase activity, and symptom scores, respectively, while following NPC 567-bradykinin challenge, these values were 174 +/- 51-mu-g ml-1, 12.3 +/- 4.1 counts min-1 x 10(-3), and 3.1 +/- 0.7. Again, no significant differences were noted. 4 We conclude that NPC 567 had no effect upon the response to nasal provocation with bradykinin. Possible explanations for the lack of effect of NPC 567 include low potency of the drug or the presence of different kinin receptors in the nasal mucosa.