RRC ID 67907
Author Tanaka K, Ishihara T, Sugizaki T, Kobayashi D, Yamashita Y, Tahara K, Yamakawa N, Iijima K, Mogushi K, Tanaka H, Sato K, Suzuki H, Mizushima T.
Title Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease.
Journal Nat Commun
Abstract The clinical treatment of chronic obstructive pulmonary disease (COPD) requires not only an improvement of airflow by bronchodilation but also the suppression of emphysema by controlling inflammation. Here we screen a compound library consisting of clinically used drugs for their ability to prevent elastase-induced airspace enlargement in mice. We show that intratracheal administration or inhalation of mepenzolate bromide, a muscarinic antagonist used to treat gastrointestinal disorders, decreases the severity of elastase-induced airspace enlargement and respiratory dysfunction. Although mepenzolate bromide shows bronchodilatory activity, most other muscarinic antagonists do not improve elastase-induced pulmonary disorders. Apart from suppressing elastase-induced pulmonary inflammatory responses and the production of superoxide anions, mepenzolate bromide reduces the level of cigarette smoke-induced airspace enlargement and respiratory dysfunction. Based on these results, we propose that mepenzolate bromide may be an effective therapeutic for the treatment of COPD due to its anti-inflammatory and bronchodilatory activities.
Volume 4
Pages 2686
Published 2013-1-1
DOI 10.1038/ncomms3686
PII ncomms3686
PMID 24189798
MeSH Administration, Inhalation Animals Anions Anti-Inflammatory Agents / pharmacology* Benzilates / pharmacology* Bronchoalveolar Lavage Bronchodilator Agents / pharmacology* Disease Models, Animal Dose-Response Relationship, Drug Female Inflammation / drug therapy Infusions, Parenteral Lung / metabolism Lung / physiopathology Male Mice Mice, Inbred DBA Mice, Inbred ICR NADPH Oxidases / metabolism NF-kappa B / metabolism Pancreatic Elastase / adverse effects Pancreatic Elastase / antagonists & inhibitors Piperidines / pharmacology* Pulmonary Disease, Chronic Obstructive / drug therapy* Pulmonary Emphysema / drug therapy Superoxides / chemistry Swine Time Factors
IF 12.121
Human and Animal Cells RAW 264(RCB0535)