Effects of the non-peptide B-2 receptor antagonist FR173657 in models of visceral and cutaneous inflammation

Objective: The non-peptide B-2 receptor antagonist (E)-3-(6-acetamido-3-pyr idyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinolinyl)oxymethyl]phenyl]-N-meth ylaminocarbonylmethyl]acrylamide (FR173657) was compared to the peptide ant agonist icatibant in models of visceral and cutaneous inflammation. Methods: Pancreatitis was induced by caerulein in anaesthetized Sprague-Daw ley rats. Acute cystitis was induced by intravesical instillation of xylene or i.p. cyclophosphamide injection. Cutaneous inflammation was induced in anaesthetized guinea-pigs by s.c. injection of collagenase from Clostridium histolyticum. Results: FR173657 inhibited oedema formation and tissue enzyme retention du ring pancreatitis at 500 nmol/kg and above after peroral administration, an d from 30 nmol/kg after s.c. injection; icatibant was effective at 3 nmol/k g s.c. Protein extravasation in both cystitis models was abolished by s.c. FR173657 at 300 nmol/kg. Collagenase-induced oedema was attenuated equieffe ctively by FR173657 and icatibant at doses of 10 mu mol/kg and 300 nmol/kg s.c., respectively. Conclusions. FR173657 inhibits kinin-mediated effects in visceral and cutan eous inflammation at doses that are about 10 times higher than those of ica tibant. However, FR173657 is also active following oral administration.