M. Masataka et al., EFFECTS OF AN ORALLY-ACTIVE NONPEPTIDE BRADYKININ B-2 RECEPTOR ANTAGONIST, FR173657, ON PLASMA EXUDATION IN RAT CARRAGEENAN-INDUCED PLEURISY, British Journal of Pharmacology, 121(4), 1997, pp. 723-730
1 Effects of an orally active non-peptide (BK) B-2 receptor antagonist
, FR173657 nyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl] acrylami
de) on the plasma exudation in rat carrageenin-induced pleurisy were i
nvestigated. 2 Plasma exudation induced by intrapleural injection of b
radykinin (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
. 3 The inhibitory effect of 30 mg kg(-1) FR173657 persisted for more
than 4 h. 4 Intrapleural injection of lambda-carrageenin (2% (w/v), 0.
1 ml per rat) caused marked plasma exudation and accumulation of exuda
tes 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) significant
ly (by 50-77%) blunted the plasma exudation 1, 3, 5, and 7 h after car
rageenin, causing a significant parallel reduction (by 42-57%) in the
volume of exudates. 5 The anti-inflammatory effect of FR173657 on rat
carrageenin-induced pleurisy was almost equipotent with that of the pe
ptide B-2 antagonist Hoe140 (1 mg kg(-1), i.v.), a plasma kallikrein i
nhibitor, soy bean trypsin inhibitor (0.3 mg per rat, intrapleural inj
ection) and bromelain (10 mg kg(-1), i.v.). 6 In pleurisy induced by i
ntrapleural injection of a histamine releaser, compound 48/80, the pla
sma exudation was observed only within 20 min after the injection. Thi
s plasma exudation was not affected by FR173657, although it was compl
etely inhibited by a mixture of pyrilamine (5 mg kg(-1), i.v.) and met
hysergide (3 mg kg(-1), i.v.). 7 These results indicate that FR173657
is an orally active, promising anti-inflammatory agent for kinin-depen
dent inflammation.