Disease relevance of FR173657

• Hyperalgesia induced by prostaglandin E2 remained unaffected by FR173657 [1].
• Effects of FR173657, a non-peptide B2 antagonist, on kinin-induced hypotension, visceral and peripheral oedema formation and bronchoconstriction [2].
• Results: In the type I allergy model, FR173657 inhibited 34% of the early-phase VPE, which occurs a few minutes after antigen injection, and 50% of the subsequent swelling at the allergic reaction sites [3].
• FR173657 (4 mg/kg body weight) was administered orally 30 min before antigen injection [3].
• Bradykinin B2 receptor antagonist FR173657 ameliorates small bowel ischemia-reperfusion injury in dogs [4].

High impact information on FR173657

• FR167344 and FR173657 inhibited the B2 receptor-mediated phosphatidylinositol (PI) hydrolysis and produced a concentration-dependent rightward shift in the dose-response curve to bradykinin [5].
• Estimated pA2 values for the antagonism of bradykinin-induced PI hydrolysis by FR167344 and FR173657 were 8.0 and 9.0, respectively [5].
• MEN16132, and the other reference antagonists, inhibited only one portion of BK specific binding, and the rank order of potency was (pIC(50)): Icatibant (lung 10.7; ileum 10.2)=MEN11270 (lung 10.4; ileum 9.9)=MEN16132 (lung 10.5; ileum 9.9). > LF16-0687 (lung 8.9; ileum 8.8) > FR173657 (lung 8.6; ileum 8.2) [6].
• 2. To this end we have tested the effects of the B2 receptor antagonists Hoe 140, FR173657 or FR172357 on the pleural inflammatory response triggered by intrapleural (i.pl.) injection of allergen (ovalbumin, 12 microg cavity(-1)) in 14 day-actively sensitized Wistar rats [7].
• FR173657 had no effect on B1 receptor-mediated relaxations in response to des-Arg9-BK [8].

Chemical compound and disease context of FR173657

• Inhibition of guinea pig skin allergic reactions by nonpeptide bradykinin B2 receptor antagonist FR173657 [3].

Biological context of FR173657

• FR167344 and FR173657 showed no stimulatory effects on PI hydrolysis [5].
• 3. In human lung fibroblast IMR-90 cells, FR173657 displaced [3H]-BK binding to B2 receptors with an IC50 of 2.9 x 10(-9) M and a Ki of 3.6 x 10(-10) M, but did not reduce [3H]-des]Arg10-kallidin binding to B1 receptors [9].
• Effects of the non-peptide B2 antagonist FR173657 on kinin-induced smooth muscle contraction and relaxation, vasoconstriction and prostaglandin release [8].
• In comparison, 5-hydroxytryptamine (1-1000 nM) facilitated peristalsis (EC50=37.7+/-23.0 nM; maximum reduction of the pressure threshold for peristalsis was approximately 76 Pa), as did FR173657 at 100 nM (reducing the pressure threshold for peristalsis by approximately 15 Pa; P<0.05) but icatibant at 10 nM was inactive (P>0.05) [10].
• In SD, shortening of the colon and reduction in hematocrit were also observable, and both were blunted by FR173657 [11].

Anatomical context of FR173657

• 2. Contractions of the isolated ileum of the guinea-pig in response to BK were inhibited by FR173657 (10-300 nM) in a concentration-dependent manner [8].
• FR173657 was a competitive antagonist in the rat uterus but showed a deviation from competitive inhibition in the other preparations studied similar to other second generation peptide antagonists [8].
• 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 [12].
• 3. The concentration-response curves for B2 receptor-mediated relaxations of the rat isolated duodenum induced by BK were shifted to the right together with a concomitant reduction of the maximum BK effect in the presence of FR173657 (10-300 nM) [8].
• In sensitized guinea pigs pretreated with phosphoramidon, FR173657 (20 mg/kg, p.o.) inhibited plasma extravasation evoked by ovalbumin aerosol (5%, 2 min) by 77+/-14.2% in the trachea and 65+/-11.2% in the main bronchi [13].

Associations of FR173657 with other chemical compounds

• 4. In guinea-pig isolated preparations, FR173657 antagonized BK-induced contractions with an IC50 of 7.9 x 10(-9) M, but did not antagonize acetylcholine or histamine-induced contractions even at a concentration of 10(-6) M [9].
• 1. Effects of an orally active non-peptide (BK) B2 receptor antagonist, FR173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinoli nyl) oxymethyl]phenyl]-N-methylaminocarbonylmethyl] acrylamide) on the plasma exudation in rat carrageenin-induced pleurisy were investigated [12].
• The latency in B/N-Kitasato rat was prolonged by administration of a bradykinin (BK) B2 receptor antagonist, FR173657 (30 mg/kg, p.o.), whereas it was shortened by pretreatment with a kininase II inhibitor, captopril (10 mg/kg, i.p.). Both agents did not affect the latency in B/N-Katholiek rats [14].

Gene context of FR173657

• Oral administration of a B2 receptor antagonist, FR173657 (30 mg/kg/day), significantly suppressed the vascular permeability, but a B1 antagonist, desArg10-Hoe140 (1 mg/kg/day) did not [15].
• Two potent B2 receptor antagonists, FR173657 (1 and 100 nM) and icatibant (10 nM), significantly antagonized the inhibitory action of serosally applied bradykinin on peristalsis (P<0.01), whilst the B1 receptor antagonist, Lys-[des-Arg9, Leu8]-bradykinin (100 nM) was inactive (P>0.05) [10].

Analytical, diagnostic and therapeutic context of FR173657

• BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on ischemia-reperfusion (I/R) injury in a canine lung transplantation model [16].

References