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Effects of an orally active non‐peptide bradykinin B 2 receptor antagonist, FR173657, on plasma exudation in rat carrageenin‐induced pleurisy
Author(s) -
Majima Masataka,
Kawashima Noriko,
Hiroshi Ito,
Katori Makoto
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701194
Subject(s) - bradykinin , antagonist , pleurisy , receptor antagonist , pharmacology , chemistry , endocrinology , receptor , medicine , carrageenan , oral administration , histamine , pleural effusion
Effects of an orally active non‐peptide (BK) B 2 receptor antagonist, FR173657 ((E)‐3‐(6‐acetamido‐3‐pyridyl)‐ N‐[N‐[2,4‐dichloro‐3‐[(2‐methyl‐8‐quinolinyl)oxymethyl]phenyl]‐N‐methylaminocarbonylmethyl] acrylamide) on the plasma exudation in rat carrageenin‐induced pleurisy were investigated. Plasma exudation induced by intrapleural injection of bradykinin (BK, 3 nmol per rat) into male SD strain rats (SPF, 8 weeks old) were significantly inhibited by oral administration of novel B 2 receptor antagonist FR173657 (3–30 mg kg −1 , 1 h before BK injection) in a dose‐dependent manner, whereas that induced by histamine was not. The inhibitory effect of 30 mg kg −1 FR173657 persisted for more than 4 h. Intrapleural injection of λ‐carrageenin (2% (w/v), 0.1 ml per rat) caused marked plasma exudation and accumulation of exudates from 1 h after carrageenin injection. The maximum plasma exudation response was observed 5 h after carrageenin. The oral administration of FR173657 to rats (30 mg kg −1 , 1 h before carrageenin) significantly (by 50–77%) blunted the plasma exudation 1, 3, 5, and 7 h after carrageenin, causing a significant parallel reduction (by 42–57%) in the volume of exudates. The anti‐inflammatory effect of FR173657 on rat carrageenin‐induced pleurisy was almost equipotent with that of the peptide B 2 antagonist Hoe140 (1 mg kg −1 , i.v.), a plasma kallikrein inhibitor, soy bean trypsin inhibitor (0.3 mg per rat, intrapleural injection) and bromelain (10 mg kg −1 , i.v.). In pleurisy induced by intrapleural injection of a histamine releaser, compound 48/80, the plasma exudation was observed only within 20 min after the injection. This plasma exudation was not affected by FR173657, although it was completely inhibited by a mixture of pyrilamine (5 mg kg −1 , i.v.) and methysergide (3 mg kg −1 , i.v.). These results indicate that FR173657 is an orally active, promising anti‐inflammatory agent for kinin‐dependent inflammation.British Journal of Pharmacology (1997) 121 , 723–730; doi: 10.1038/sj.bjp.0701194