Effects of the non-peptide B2 receptor antagonist FR173657 in models of visceral and cutaneous inflammation.
OBJECTIVE
The non-peptide B2 receptor antagonist (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinolin yl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide (FR173657) was compared to the peptide antagonist icatibant in models of visceral and cutaneous inflammation.


METHODS
Pancreatitis was induced by caerulein in anaesthetized Sprague-Dawley 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 during pancreatitis at 500 nmol/kg and above after peroral administration, and from 30 nmol/kg after s.c. injection; icatibant was effective at 3 nmol/kg s. c. Protein extravasation in both cystitis models was abolished by s.c. FR173657 at 300 nmol/kg. Collagenase-induced oedema was attenuated equieffectively by FR173657 and icatibant at doses of 10 micomol/kg and 300 nmol/kg s.c., respectively.


CONCLUSIONS
FR173657 inhibits kinin-mediated effects in visceral and cutaneous inflammation at doses that are about 10 times higher than those of icatibant. However, FR173657 is also active following oral administration.
Griesbacher
T
T
Department of Experimental and Clinical Pharmacology, University of Graz, Austria. thomas.griesbacher@kfunigraz.ac.at
Legat
F J
FJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001798:Blood Proteins / Q000378:metabolism; D065168:Bradykinin Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects; D003556:Cystitis / Q000188:drug therapy; D003872:Dermatitis / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D010195:Pancreatitis / Q000188:drug therapy; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D065168:Bradykinin Receptor Antagonists; C105311:FR 173657; D011804:Quinolines; D043782:Receptor, Bradykinin B2