Disease relevance of Lodoxamide

• The protective effect of lodoxamide on antigen-induced bronchospasm. An orally active antiallergic drug [1].
• Effect of lodoxamide on the secretory response induced by Escherichia coli and Vibrio cholerae enterotoxins in infant mice [2].
• Mechanisms and comparison of anti-allergic efficacy of topical lodoxamide and cromolyn sodium treatment in vernal keratoconjunctivitis [3].
• Lodoxamide (0.01-20 mg kg-1) also blocked selectively but incompletely the response to APNEA [4].
• The antiallergic compound, lodoxamide, was evaluated for its abilities to attenuate a local allergic reaction in rat conjunctiva in vivo and to inhibit rat conjunctival mast cell mediator release in vitro [5].

High impact information on Lodoxamide

• The mast cell stabilizer, lodoxamide, an H1- (but not an H2-) receptor antagonist, and diamine oxidase (histaminase) were also effective in reducing the LAE and albumin leakage elicited by Tx-A [6].
• The exacerbated response in W/Wv mice was greatly attenuated by pretreatment with either dexamethasone (1.3-fold) or the selective inducible NOS inhibitor, aminoguanidine (1.4-fold), and partially attenuated by the mast cell stabiliser, lodoxamide (2.9-fold) [7].
• The ability of lodoxamide to stabilize mast cells was confirmed by histological examination [8].
• Twenty-four hours after removal of the tourniquet, saline-treated gastrocnemius muscle had a mean viability of 14% compared with 28% (p<0.05) and 48% (p<0.01) after 25 mg/kg and 75 mg/kg of lodoxamide treatment, respectively [8].
• Further studies are warranted to compare the effectiveness of lodoxamide with that of cromolyn sodium in protection against antigen-induced bronchospasm and to evaluate the relative efficacy and safety of lodoxamide in long-term clinical trials [9].

Chemical compound and disease context of Lodoxamide

• Efficacy of lodoxamide eye drops on mast cells and eosinophils after allergen challenge in allergic conjunctivitis [10].
• Exposed mice developed allergic conjunctivitis clinically and histologically that was modulated by topical lodoxamide, cromolyn, livocarbastine, or nedocromil eye drops or TDR intraperitoneally injected [11].
• Allopurinol and lodoxamide in complement-induced hepatic ischemia [12].
• Comparison of topical 0.05% levocabastine and 0.1% lodoxamide in patients with allergic conjunctivitis. Study Group [13].
• The injection of lodoxamide (a purported inhibitor of histamine release) inhibited compound 48/80-induced hypotension at all doses except 1 mg/kg [14].

Biological context of Lodoxamide

• Those subjects demonstrating a protective effect of lodoxamide subsequently underwent antigen inhalation challenges at various time intervals (2 to 8 hr) after lodoxamide treatment [9].
• Lodoxamide was highly effective, as judged by the absence of both overt signs and characteristic post-DEC changes in platelet numbers, serum fibrinogen level, and serum transaminase (SGOT, SGPT) levels, in blocking the reaction in dogs with a microfilaremia level that would make them moderately reactive [15].
• Furthermore, the inhibitory effects of FR50948 on type III reactions and inflammatory reactions were much more potent than those of SCG and equal to those of lodoxamide, and the effect on IgG-mediated PCA was stronger than that of either reference drug [16].
• RESULTS: Only levacobastine and lodoxamide decreased vascular permeability at a significant ratio (46%, p < 0.01 and 31%, p < 0.05, respectively) [17].
• Although infusion of 1.0 microgram per 100 g b.w. serotonin and/or 10 micrograms per 100 g b.w. lodoxamide produced no change in arterial blood pressure, 10 or 20 micrograms per 100 g b.w. serotonin evoked hypotension within 40 sec [18].

Anatomical context of Lodoxamide

• RESULTS: Lodoxamide significantly reduced tryptase levels (P < 0.01), neutrophils (P < 0.04), and eosinophils (P < 0.01) in the tear fluid and significantly inhibited ocular itching (P < 0.02) when compared with that of placebo [10].
• These results suggest lodoxamide may be useful in alleviating ischemic damage to the spinal cord [19].
• Moreover, lodoxamide was able to downregulate in vitro ICAM-1 expression on the continuously cultured, differentiated conjunctival cell line WK [20].
• Effects of lodoxamide on ischemic reperfused myocardium [21].
• Lodoxamide was infused 20 mg/kg/h i.v. starting 30 min before occlusion of the proximal left circumflex coronary artery (LCX) and continuing through 90 min of ischemia [21].

Associations of Lodoxamide with other chemical compounds

• To determine further the role of mast cells in IR injury, wild-type mice were treated 30 min prior to reperfusion with an intraperitoneal dose of either saline or the mast cell-stabilizing agent lodoxamide trometamol (2.5, 7.5, 25 or 75 mg/kg) [8].
• Two mast-cell stabilizers, cromolyn and lodoxamide, markedly reduced NE release, implicating cardiac mast cells as a major source of chymase [22].
• Moreover, the mean level of radioactivity in the ketotifen- and lodoxamide-treated eyes was comparable with the mean level of radioactivity in the saline-treated eye of Group 1, which had not been exposed to allergen [23].
• In 3 of these animals, we attempted to blunt the CBE response with chlorpheniramine (0.1 mg/kg i.v.) and a mast cell stabilizer lodoxamide (0.1 mg/ml aerosol) [24].
• Furthermore, pretreatment of rats with the CRF antagonist alpha-helical CRF9-41, hexamethonium, or the mast cell stabilizer lodoxamide inhibited our observed colon responses to immobilization stress [25].

Gene context of Lodoxamide

• The simultaneous administration of lodoxamide with ST or CT enterotoxin resulted in a significant (P less than 0.01) inhibition of the intestinal fluid response [2].
• Lodoxamide was also able to strongly inhibit the release of eosinophil peroxidase after IgA-dependent activation and, to a lesser extent, the release of eosinophil cationic protein and eosinophil-derived neurotoxin [26].
• The chemotactic response of eosinophils to fMLP as well as to IL-5, in vitro, was very significantly and dose-dependently inhibited by Lodoxamide [26].
• CONCLUSIONS: In patients with VKC, lodoxamide significantly reduced ECP tear levels, and thus, eosinophil activation, and was more effective than DSCG in reducing clinical signs and symptoms [27].
• Platelet-leukocyte aggregates and mast cell degranulation induced by I/R were also attenuated by administration of either superoxide dismutase or lodoxamide [28].

Analytical, diagnostic and therapeutic context of Lodoxamide

• All subjects underwent antigen inhalation challenge 15 min after inhalation of an aerosolized solution of 0.1 mg of lodoxamide in saline or of saline solution alone (placebo) administered on separate days according to a double-blind, random-allocation protocol [9].
• Determination of lodoxamide in plasma using ion-pairing and reversed-phase high-performance liquid chromatography [29].
• Lodoxamide produced a significant reduction in ultimate infarct size measured at 24 h by postmortem tetrazolium perfusion staining [21].
• Albumin concentrations in lavage fluid (BAL) of lodoxamide-treated animals were 243 +/- 165 micrograms/ml in right lung and 29 +/- 15 micrograms/ml in left lung (p less than 0.03); albumin concentration in right lung BAL of untreated animals was 1,180 +/- 319 micrograms/ml (p less than 0.02 vs. lodoxamide-treated animals) [30].
• After treatment with lodoxamide 0.1%, tear LTB4 and LTC4 levels of the OP-GPC patients decreased significantly [31].

References