Disease relevance of Rev 5901

• Whereas treatment with a 5-lipoxygenase inhibitor, PF-5901 (100 mg/kg PO), resulted in a significant reduction of the severity of colitis, concomitant administration of PF-5901 and indomethacin (0.5 mg/kg SC) did not inhibit the exacerbative effects of the indomethacin in this model [1].
• In the second study, groups of rats were orally pretreated with PF-5901 (100 mg/kg) or vehicle 3 or 12 h prior to induction of endotoxic shock by i.v. administration of lipopolysaccharide from Salmonella typhosa [2].
• PF-5901 significantly reduced the hemoconcentration, but not the hypotension associated with endotoxic shock [2].
• In the third protocol we gave RG 5901, a relatively specific 5-lipoxygenase inhibitor, to 5 dogs with lobar atelectasis [3].
• The pressor response to hypoxia was +8.9 +/- 2.1 mmHg before and +8.7 +/- 3.7 mmHg after RG 5901 (p greater than 0.05) [3].

High impact information on Rev 5901

• In addition, the 5-lipoxygenase inhibitor RG 5901 (1 or 10 mg/kg i.v.) produced a two-thirds attenuation in PAF priming [4].
• Described in this first report are the structure-activity relationships that led to a more than a 20-fold improvement of the potency and selectivity of the initial chemical lead (RG 5901) [5].
• On the other hand, the leukotriene (LT) B(4) receptor antagonist U-75302, the LTD(4) receptor antagonists LY-171883 and MK-571, and the cysteinyl-LT receptor antagonist REV-5901 also inhibit cell proliferation and [(3)H]-thymidine incorporation in a concentration-dependent manner, and delay the RAW 264.7 cell cycle [6].
• However, the pulmonary infiltration of neutrophils and eosinophils induced by antigen was unaltered by prior treatment with PF 5901 (10 mg) [7].
• 2. While PF 5901 (10 mg) had no significant effect on the acute bronchoconstriction induced by antigen, this dose was sufficient to inhibit significantly the increase in airway responsiveness to inhaled histamine 24 h following antigen challenge (P < 0.05) [7].

Biological context of Rev 5901

• REV-5901 also inhibited the calcium ionophore-induced release of immunoreactive leukotrienes from human lung in vitro with IC50 values of 11.7 +/- 2.2 MicroM versus peptide leukotrienes and 10.0 +/- 1.1 microM versus iLTB4 [8].
• The physicochemical basis of improvement of the bioavailability of a poorly water-soluble drug [REV 5901; alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; 1] after oral administration as organic solutions was investigated [9].
• The indices of hypoxic vasoconstriction were not affected by RG 5901 [3].

Anatomical context of Rev 5901

• To clarify further the protective mechanism of lipoxygenase inhibitors, we have examined the effects of two nonantioxidant inhibitors, SK&F 86002 and REV-5901, on human neutrophil activation and function in vitro [10].
• 3. The release of PAF by peritoneal mast cells could be inhibited, in a concentration-dependent manner, by PF-5901 (IC50 of 3.9 microM) or Wy-50,295 (IC50 of 1.2 microM), two structurally similar compounds with inhibitory effects on leukotriene synthesis, as well as leukotriene D4 (LTD4) receptor antagonist properties [11].
• The lipoxygenase inhibitors nordihydroguaiaretic acid, B755C, Rev 5901 and AA861 antagonized responses to LTE4 in the presence, but not in the absence of epithelium [12].
• Neutrophil infiltration into the ischaemic/reperfused rabbit isolated myocardium: effect of PF-5901 and cycloheximide [13].
• REV-5901 (10 + 2 mg/kg i.v.) reduces infarct size produced by coronary artery occlusion and reperfusion in the anesthetized dog from 56.6 +/- 2 to 28.6 +/- 3.7% of the hypoperfused zone [14].

Associations of Rev 5901 with other chemical compounds

• Its formation was inhibited by 5,8,11,14-eicosatetraynoic acid, but not by indomethacin or a specific 5-lipoxygenase inhibitor (REV 5901) [15].
• The lack of effect on TxB2 and 6-keto-PGF1 alpha indicates that REV-5901 did not inhibit phospholipase A2, cyclooxygenase, or thromboxane synthetase [8].
• Of the 5-lipoxygenase inhibitors investigated, MK-886(3-(1-(4-chlorobenzyl)-3-tert-butyl-thio-5-isopropylindol-2- yl)-2,2 -dimethyl propanoic acid), L-656,224 ((7-chloro-2-[4-methoxypenyl]methyl)-3 -methyl-5-propyl-4-benzofuranol), PF-5901 and tepoxalin were the most potent inhibitors of IL-1 production [16].
• MK 571, LY 171883, BAY u9773 (CysLT receptor antagonists) and REV 5901 (a CysLT receptor antagonist and a 5-LO inhibitor) were equally effective in inhibiting 5-HT-induced PE, indicating that leukotrienes mediate 5-HT-induced PE via CysLT receptors [17].
• REV 5901 and Ly 171,883 protect rat gastric mucosa against ethanol-induced damage [18].

Gene context of Rev 5901

• The 5-lipoxygenase inhibitor REV-5901 [alpha-pentyl-3-(2-quinolinylmethoxy)benzene-methanol] was evaluated for effects on mediator release in vitro from fragmented guinea-pig and human lung [8].

Analytical, diagnostic and therapeutic context of Rev 5901

• 3. Total leucocyte infiltration into the airways induced by antigen, as assessed by bronchoalveolar lavage, was significantly inhibited by pretreatment with PF 5901 (10 mg) [7].

References