Pharmacodynamic Study Of Compound CT133 On Allergic Asthma

Background and Objective:The pathogenesis of asthma has not yet been fully understood. The studies have been shown that using of the CRTH2 selective antagonists can effectively improve the symptoms and signs of asthma and allergic rhinitis. Related animal experiments show that CRTH2 receptor antagonists can improve airway pathology in animal model of asthma, reduce the infiltration of eosinophils in the airways and relieve the airway inflammation. Compound CT133 is a new synthesized compound, which is a CRTH2 receptor antagonist. We hypothesize that compound CT133 has a certain effect on asthma therapy.Methods:According to the reference clinical dosage and preliminary experimental results, we designed groups by the Factorial analysis method, including normal control group, model group, compound CT133 drug delivery groups and positive drug group. Asthma model was induced by OVA in mice/guinea pigs. After treatment for 7 days,18 hours after the last drug administration, the mice/guinea pigs were sacrificed for sample collection. This study gets the results by detecting airway inflammation, lung histopathological analysis and pulmonary function.Results:1. Compared with the control group, the model group indicated:Total number of inflammatory cells in BALF, differential leukocyte count and classification and inflammatory infiltration around the airway was all significantly increased, goblet cell metaplasia, decreased lung compliance and increased lung resistance.2. Compared with the control group, compound CT133 (3,10,30mg/kg) inhibits the infiltration of inflammatory cells in animal model of asthma and cytokine expression of IL-4 and IL-5. CT133 (6,18 mg/kg) has the same effects on asthma in the guinea pig model.3. Compound CT133 (10,30mg/kg) improves airway hyperreactivity in OVA induced asthma model of mice. CT133 also inhibits the Mch induced increasing of lung resistance and decreasing of lung compliance in asthma model of guinea pig.Conclusion:Compound CT133 can not only significantly inhibits airway inflammation, but also significantly improve the pulmonary function of in asthma model of mice and guinea pig. The results will be effective in delaying the progression of asthma, and provide new ideas for the treatment of asthma. It has a potential practical and theoretical value.