title: Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease.
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.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105 8512, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ishihara
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Sugizaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tahara
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamakawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Iijima
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Keizo
authors.initials: K
authors.lastname: Sato
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000838:Anions; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001561:Benzilates / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000188:drug therapy; D007263:Infusions, Parenteral; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010196:Pancreatic Elastase / Q000009:adverse effects / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011656:Pulmonary Emphysema / Q000188:drug therapy; D013481:Superoxides / Q000737:chemistry; D013552:Swine; D013997:Time Factors
chemical_list: D000838:Anions; D000893:Anti-Inflammatory Agents; D001561:Benzilates; D001993:Bronchodilator Agents; D016328:NF-kappa B; D010880:Piperidines; D013481:Superoxides; C005101:mepenzolic acid; D019255:NADPH Oxidases; D010196:Pancreatic Elastase