Disease relevance of AIDS-128973

• Failure of doxantrazole in steroid-sensitive nephrotic syndrome [1].
• Pretreatment with mast cell stabilizers ketotifen (1 mg/kg, p.o.) or doxantrazole (5 mg/kg, i.p.) prevented both manipulation-induced inflammation and gastroparesis [2].
• To determine the involvement of colonic NGF overexpression and mast cell hyperplasia in visceral hyperalgesia induced by MD, neonatally deprived adult rats received anti-NGF antibodies or doxantrazole [3].
• The reagents Doxantrazole and the mAb G63, which suppress mast cell secretory responses, also prevented the rise in rat mast cell protease II and significantly reduced the early vasculitis [4].
• Doxantrazole did not modify the hypersensitivity to GD but prevented mast cell degranulation [5].

High impact information on AIDS-128973

• The myoelectric disturbance in both colon and jejunum was inhibited significantly by pretreatment with atropine and hexamethonium, doxantrazole, cyclooxygenase, and lipoxygenase inhibitors [6].
• RX 77368-stimulated luminal protein release was abolished by vagotomy and reduced by doxantrazole [7].
• All were inhibited by the chloride channel blocker diphenyl-2-carboxylate, by chloride-free buffer, and by doxantrazole, a mast cell stabilizer [8].
• Quercetin (10(-4) to 10(-8) mol/L) and doxantrazole (3 X 10(-4) to 10(-7) mol/L), which inhibit both rat mast cell types, also inhibit HR in both human mast cell preparations [9].
• The 8-chloro and unsubstituted analogues were more potent that cromolyn sodium and doxantrazole intravenously in the rat PCA test [10].

Chemical compound and disease context of AIDS-128973

• 2-Methyl-11-oxo-11H-pyrido[2,1-b]quinoazoline-8-carboxylic acid (6) was superior to cromolyn sodium and doxantrazole orally and intravenously in the rat PCA test and a rat allergic bronchospasm model [11].
• Cold urticaria: inhibition of cold-induced histamine release by doxantrazole [12].
• Mast cell involvement in iodoacetamide-induced gastritis was investigated in rats receiving oral administration of iodoacetamide together with the mast cell stabilizer doxantrazole (ip) or its solvent [13].
• The effect of oral doxantrazole on allergen-induced bronchospasm [14].
• The protective effect of 200 mg doxantrazole given orally on allergen-induced bronchoconstriction has been compared with 20 mg inhaled disodium cromoglycate (DSCG) in 15 patients with bronchial asthma and immediate-type hypersensitivity [14].

Biological context of AIDS-128973

• 4 These results suggest that dicumarol, like doxantrazole and theophylline, inhibits histamine release without affecting mast cell energy metabolism [15].
• In an open assessment study with the same patients, increasing the doxantrazole dose to 400 mg did not affect post-exercise bronchoconstriction [16].
• Correlation of bioavailability in man with simulated absorption data for three doxantrazole preparations [17].
• Inhibitory effect of oral doxantrazole on asthma induced by allergen inhalation [18].

Anatomical context of AIDS-128973

• RESULTS: Mucosal exposure of distal ileal mucosa (intact and isolated, and naive and sensitized) to FMLP was associated with an increase in permeability to dextran 4400, which was completely ablated by morphine and doxantrazole [19].
• It is concluded that doxantrazole- and sodium cromoglycate-inhibited lucigenin-dependent chemiluminescence production by guinea-pig alveolar macrophages is due to a direct scavenging effect on reactive oxygen species [20].
• METHODS: Intact and isolated segments of distal ileum of naïve and sensitized (Trichinella spiralis and egg albumin) Sprague-Dawley rats were exposed to FMLP with or without morphine or doxantrazole, a mast cell-stabilizing agent [19].
• Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole (P less than 0.001) and the connective tissue mast cell stabilizer disodium cromoglycate (P less than 0.05) [21].

Associations of AIDS-128973 with other chemical compounds

• Antibiotics and doxantrazole (a mast cell membrane stabilizer) significantly inhibited the effect of ethanol [22].
• These results are discussed in terms of the functional heterogeneity of mast cells from different sources and identify a group of compounds other than doxantrazole (reported previously), which inhibit histamine secretion by MMC [23].
• 1 Dextran-induced release of histamine from rat mast cells was inhibited equally in complete and glucose-free Tyrode solution by doxantrazole (0.03-3 micronmol/l), theophylline (0.1-3 mmol/l) and dicumarol (0.01-10 micronmol/litre) [15].
• The activity of a mast cell stabilizer (doxantrazole), kinin antagonists (des-Arg 10-[Leu9]-kallidin, B1, HOE 140, B2) and tachykinin antagonists (CP 99, 994, NK1, SR 142801, NK3) were tested against the distension-induced depressor responses in control and post-infected rats [24].
• Doxantrazole and KNO3 significantly reduced iodoacetamide-induced increase in gastric MPO activity, increased MMC number, and decreased RMCP II serum level in basal conditions [13].

Gene context of AIDS-128973

• The effect of LPS was reduced by doxantrazole, Lys-D-Pro-Thr, and soluble recombinant TNF receptor [25].
• RESULTS: Stress and CRF enhanced the number of abdominal cramps evoked by rectal distension without affecting rectal compliance. alpha-helical CRF9-41 and doxantrazole antagonized the stress and CRF-induced enhancement of abdominal cramps [26].
• Pretreatment of sensitized tissue with doxantrazole (10(-4) M) markedly reduced Fos immunoreactivity observed after EA exposure [27].
• This augmented hyperemic response could be significantly attenuated by pretreatment with a histamine H1-receptor antagonist (pyrilamine) or with a mast cell stabilizer (doxantrazole) [28].
• Contraction was inhibited by the mast cell stabilizer doxantrazole and the 5-hydroxytryptamine (5-HT) antagonist cyproheptadine [29].

Analytical, diagnostic and therapeutic context of AIDS-128973

• A double-blind study was carried out in 3 subjects, all of whom showed diminished cold-stimulated histamine release after doxantrazole [12].
• In a double-blind cross-over trial in 13 patients with exercise-induced asthma, doxantrazole 200 mg taken orally 1 hour before a standardized exercise test involving stair climbing failed to block post-exercise bronchoconstriction [16].
• In contrast, acid perfusion induced esophageal shortening, which was abolished by pretreatment with either doxantrazole or DSCG in doses sufficient to attenuate the acid-induced mucosal histamine release [30].
• The antisecretory effect of systemic 5-HT was insensitive to pretreatment with piroxicam, doxantrazole, close gastric intra-arterial sodium nitroprusside, somatostatin monoclonal antibody, or bilateral adrenalectomy [31].

References