Lodoxamide tromethamine
(Synonyms: 洛度沙胺氨丁三醇,U-42585E) 目录号 : GC36476
A potent agonist of GPR35 and a mast cell stabilizer
Cas No.:63610-09-3
Sample solution is provided at 25 µL, 10mM.
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Lodoxamide is a potent agonist of GPR35 with an EC50 value of 1.61 nM in a β-arrestin-2 interaction assay using CHO-K1 cells expressing the human receptor.1 It inhibits histamine release induced by compound 48/80 , anti-IgE, or A23187 in isolated rat peritoneal mast cells (IC50s = 0.1-50 ?M) and inhibits A23187-induced calcium influx in mast cells.2 It reduces antigen-induced histamine release from rat conjunctival tissue by 46% in vitro when used at a concentration of 10 ?g/ml.3 Lodoxamine (0.1 and 10%, w/v) reduces the immediate hypersensitivity response in rat conjunctiva in vivo in a dose-dependent manner and reduces mast cell degranulation in a topical ovalbumin challenge.3,4 Formulations containing lodoxamide have been used in the treatment of vernal conjunctivitis and keratitis.
1.MacKenzie, A.E., Caltabiano, G., Kent, T.C., et al.The antiallergic mast cell stabilizers lodoxamide and bufrolin as the first high and equipotent agonists of human and rat GPR35Mol. Pharmacol.85(1)91-104(2014) 2.Johnson, H.G., and Sheridan, A.Q.The characterization of lodoxamide, a very active inhibitor of mediator release, in animal and human models of asthmaAgents Actions18(3-4)301-305(1986) 3.Yanni, J.M., Weimer, L.K., Glaser, R.L., et al.Effect of lodoxamide on in vitro and in vivo conjunctival immediate hypersensitivity responses in ratsInt. Arch. Allergy. Immunol.101(1)102-106(1993) 4.Bayer, A., Uluda?, H.A., Sobaci, G., et al.Comparison of antiallergic drugs in an experimental model of ocular anaphylaxisOphthalmologica217(2)119-123(2003)
| Cas No. | 63610-09-3 | SDF | |
| 别名 | 洛度沙胺氨丁三醇,U-42585E | ||
| Canonical SMILES | N#CC1=CC(NC(C(O)=O)=O)=C(Cl)C(NC(C(O)=O)=O)=C1.OCC(CO)(N)CO.OCC(CO)(N)CO | ||
| 分子式 | C19H28ClN5O12 | 分子量 | 553.9 |
| 溶解度 | DMSO: 20 mg/mL (36.11 mM and warming) | 储存条件 | Store at -20°C |
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| 1 mM | 1.8054 mL | 9.0269 mL | 18.0538 mL |
| 5 mM | 0.3611 mL | 1.8054 mL | 3.6108 mL |
| 10 mM | 0.1805 mL | 0.9027 mL | 1.8054 mL |
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Lodoxamide tromethamine prevents neutrophil accumulation in reexpansion pulmonary edema
J Cardiovasc Pharmacol 1989 Aug;14(2):227-32.PMID:2476595DOI:10.1097/00005344-198908000-00007.
Reexpansion pulmonary edema (RPE) is an acute, unilateral lung injury initiated by cytotoxic oxygen metabolites and temporally associated with an influx of polymorphonuclear neutrophils (PMNs); these toxic oxygen products appear to result from reoxygenation of chronically collapsed lung. Lodoxamide tromethamine (U-42585E) reduces infarct size after reperfusion of ischemic myocardium. The possible protective effects of lodoxamide in RPE were examined. Right lungs of rabbits were collapsed for 7 days by injection of air into the pleural space. Reexpansion was accomplished by chest tube with negative pressure in spontaneously ventilating rabbits. Twelve pairs of animals received either lodoxamide (20 mg/kg/h intravenously (i.v.) from 30 min before reexpansion until they were killed) or an equivalent volume of sterile saline. After 2 h, animals were killed by i.v. pentobarbital. Right and left lungs of six pairs of animals were lavaged with 25 ml saline each; the remaining six pairs of animals were studied by measurement of lung wet/dry weight ratio. 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). PMN percentages in right BAL (3.8 +/- 3.1) and left BAL (2.9 +/- 2.2) did not differ in lodoxamide-treated animals (p greater than 0.65); PMN percentage in right BAL of untreated animals was 18.7 +/- 2.9 (p less than 0.001 vs. lodoxamide-treated animals).(ABSTRACT TRUNCATED AT 250 WORDS)
Lodoxamide tromethamine treatment for superior limbic keratoconjunctivitis
Am J Ophthalmol 1995 Sep;120(3):400-2.PMID:7661218DOI:10.1016/s0002-9394(14)72177-4.
Purpose: We studied the efficacy of topically applied Lodoxamide tromethamine 0.1% in the treatment of superior limbic keratoconjunctivitis. Methods: Three patients with clinical findings of bilateral superior limbic keratoconjunctivitis. were treated with topical Lodoxamide tromethamine four times daily in both eyes. Results: While the patients were taking Lodoxamide tromethamine, symptoms and objective findings resolved. Conclusions: Topically applied Lodoxamide tromethamine 0.1% is useful in the treatment of superior limbic keratoconjunctivitis. There may be a role for mast cell stabilizers in the treatment of this disorder.
Protective effect opf Lodoxamide tromethamine on allergen inhalation challenge
J Allergy Clin Immunol 1980 Oct;66(4):286-94.PMID:7419830DOI:10.1016/0091-6749(80)90023-8.
Lodoxamide tromethamine (U-42,585E) is a new drug intended for prophylaxis of mast cell-mediated allergic disease. It is a water-soluble, cromolyn-like agent with demonstrated activity in rat peritoneal mast cell assay, rat percutaneous anaphylaxis (rat PCA) and sensitized rhesus monkey airway system. Ten allergen-sensitive asthmatics were pretreated with lodoxamide (0.01, 0.1, or 1.0 mg) or placebo, then challenged with serial dilutions of allergen extract. Analysis of allergen dose-response curve parameters shows that pretreatment with lodoxamide offers significant protection against experimental allergen-induced bronchoconstriction. At 0.01 mg, lodoxamide was effective in over half the subjects tested. Administration of lodoxamide by inhalation at doses of 0.1 and 1.0 mg uniformly allowed subjects to tolerate significantly larger doses of inhaled allergen. Side effects observed at these doses were minimal.
Prevention of ischemia-reperfusion injury by the allergy drug Lodoxamide tromethamine
Ann Thorac Surg 1991 Oct;52(4):832-8.PMID:1929638DOI:10.1016/0003-4975(91)91220-p.
Lodoxamide tromethamine, an orphan antiallergy drug, inhibits degranulation of mast cells that reside in the myocardium and inhibits xanthine oxidase located in myocytes and predominantly in the vascular endothelium. The hypothesis evaluated was that Lodoxamide tromethamine would attenuate oxygen free radical damage. Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing 0, 1, 10, 100, or 1,000 mumol/L Lodoxamide tromethamine at 37 degrees and 24 degrees C with ischemic times of 22 and 93 minutes, respectively. These ischemic intervals yielded 50% survival and 50% return of function in untreated hearts. Lodoxamide treatment alone at the onset of reperfusion was also studied. Performance end points were aortic flow, pressure, and coronary flow. Biochemical analyses included serotonin collected from coronary effluent as a marker of mast cell degranulation, uric acid for xanthine oxidase inhibition, myocardial adenosine triphosphate, and carbonyl group concentrations. Performance data demonstrated that lodoxamide was beneficial in a log-linear dose response when given continuously at both temperatures. Percent of preischemic values for untreated and maximal responses at 1,000 mumol/L of lodoxamide were as follows: a mortality of 50% in nontreated hearts versus 0%; aortic flow, 47% to 94% (37 degrees C), 46% to 86% (24 degrees C); cardiac output, 60% to 98% (37 degrees C), 58% to 97% (24 degrees C); adenosine triphosphate, 59% to 90% (37 degrees C), 48% to 65% (24 degrees C). Serotonin was undetectable from any hearts. Uric acid concentrations and carbonyl group content did not change with increasing dose. Lodoxamide demonstrated no benefit when given only during reperfusion, suggesting injury occurred at times other than reperfusion.
Inhaled Lodoxamide tromethamine in the treatment of perennial asthma: a double-blind placebo-controlled study
J Allergy Clin Immunol 1985 Jul;76(1):83-90.PMID:4008815DOI:10.1016/0091-6749(85)90808-5.
The efficacy of Lodoxamide tromethamine in the treatment of asthma was studied in a 16-week double-blind, placebo-controlled study of 68 perennial allergic subjects with asthma. Patients received either Lodoxamide tromethamine, 0.25 mg four times daily, or placebo, administered by metered-dose inhaler. Response to treatment was assessed by analyzing changes in asthma symptoms, inhaled bronchodilator requirements, and pulmonary function when compared to a 2-week baseline period. Patients treated with Lodoxamide tromethamine demonstrated an improvement in daytime breathing difficulty, cough, sputum production, and sleep (p less than 0.01 to 0.05), but improvement was not significantly different from that demonstrated by placebo-treated patients. Patients from both treatment groups were able to reduce their inhaled bronchodilators (p less than 0.01), but again no significant difference was apparent between Lodoxamide tromethamine and placebo treatment, nor were there any differences in peak expiratory flow rate or FEV1 between the two groups. Seven patients who received Lodoxamide tromethamine withdrew because of a sensation of heat and gastrointestinal symptoms. Thus, although Lodoxamide tromethamine possesses potent mast cell-stabilizing activity in vitro, we have failed to demonstrate any useful long-term effect in the treatment of mild allergic asthma.