Cysteinyl leukotrienes (CysLTs, including LTC4, LTD4, and LTE4), mainly produced by eosinophils, mast cells, and macrophages in response to a variety of stimuli activating arachidonate 5-lipoxygenase pathway, are important inflammatory mediators. CysLT1 receptor (LTR1) expresses in human lung smooth muscle cells, lung macrophages, most peripheral blood eosinophils and pregranulocytic CD34+ cells, and in subsets of monocytes and B lymphocytes. Montelukast Sodium is a potent, selective and competitive LTR1 antagonist with IC50 value < 5 nM and are currently used in the treatment of asthma. Nonsmoking patients with asthma treated with Montelukast Sodium(200mg, three times daily for 10 1/3 days) showed improvements in FEV1, compared with placebo-treated patients[5]. In C57BL/6 mice with asthma induced by chronic exposure to ovalbumin, Montelukast (6 mg/kg, once daily for 20 days) treatment significantly suppressed the increased eosinophils in bronchoalveolar lavage (BAL) fluid and lung tissue, and increased IL-5 level in BAL fluid in models[6]. It was also proved that Montelukast inhibited the diabetes-induced capillary and neuronal degeneration in streptozotocin-induced diabetes mouse model[7].
作用机制
Montelukast Sodium is a potent competing ligand for high affinity [3H]LTD4 specific binding.
Montelukast Sodium/孟鲁司特钠 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c mice
Mouse asthma model
Subcutaneous osmotic pump
1 mg/kg
From Day 73 to Day 163, lasting 90 days
To evaluate the reversal effect of Montelukast on established airway remodeling. Results showed that Montelukast significantly reduced airway smooth muscle layer thickening and subepithelial collagen deposition/fibrosis.
Am J Respir Crit Care Med. 2006 Apr 1;173(7):718-28
Mice
Laser-induced choroidal neovascularization model
Intraperitoneal injection
1 mg/kg
Daily from D0 to D6
Montelukast inhibits CYP2C8, and combined with flunarizine further enhanced CNV suppression via tumor necrosis factor-α suppression.
China, Guangdong
... 展开 >>
the first affiliated hospital, Sun Yat-sen University
Not yet recruiting
Guangzhou, Guangdong, China, 510080
Contact: Fenghong Chen, doctor 02086013560170816 chfhong@mail.sysu.edu.cn
Principal Investigator: jianbo Shi, doctor 收起 <<
China, Guangdong
... 展开 >>
the first affiliated hospital, Sun Yat-sen University
Not yet recruiting
Guangzhou, Guangdong, China, 510080
Contact: Fenghong Chen, doctor 02086013560170816 chfhong@mail.sysu.edu.cn
Principal Investigator: jianbo Shi, doctor 收起 <<
Israel
... 展开 >> Kupat Cholim Clalit
Recruiting
Lod, Israel
Contact: Al Garushi
Principal Investigator: Al Garushi, MD
Kupat Cholim Clalit
Recruiting
Ramla, Israel
Principal Investigator: Zachi Lotem
Assaf Harofeh
Recruiting
Zerifin, Israel, 70300
Contact: Berkovitch 97289779152
Principal Investigator: Mati Berkovitch, MD 收起 <<
United Kingdom
... 展开 >> GSK Investigational Site
Manchester, Lancashire, United Kingdom, M23 9LT
GSK Investigational Site
London, United Kingdom, SE1 9RT 收起 <<
United States, Illinois
... 展开 >>
Advocate Children's Hospital Oak Lawn
Recruiting
Oak Lawn, Illinois, United States, 60453
Principal Investigator: Corrie Fletcher, DO 收起 <<
United States, Florida
... 展开 >>
Nemours Children's Clinic
Recruiting
Jacksonville, Florida, United States, 32207
Contact: Mary K Warde, RN 904-697-3176 mwarde@nemours.org
Principal Investigator: Edward B Mougey, Ph.D.
Sub-Investigator: John J Lima, PharmD
Sub-Investigator: Jason E Lang, MD 收起 <<
Withdrawn(Based on input from ... 展开 >>regulatory agencies, it is not necessary to conduct this study. An ongoing study was sufficient for regulatory purposes.) 收起 <<
United States, Ohio
... 展开 >>
Bernstein Allergy Group
Recruiting
Cincinnati, Ohio, United States, 45231
Contact: Jonathan A Bernstein, MD 513-931-0775 bernsteincrc@fuse.net
Principal Investigator: Jonathan A Bernstein, MD 收起 <<
United States, Arizona
... 展开 >>
Mayo Clinic - Scottsdale
Scottsdale, Arizona, United States, 85054
United States, California
Stanford University
Stanford, California, United States, 94305
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Maryland
National Cancer Institute Experimental Transplantation & Immunology Branch
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Siteman Cancer Center at Washington University
Saint Louis, Missouri, United States, 63110
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226 收起 <<
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