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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.
AuthorsKen-Ichiro Tanaka, Tomoaki Ishihara, Toshifumi Sugizaki, Daisuke Kobayashi, Yasunobu Yamashita, Kayoko Tahara, Naoki Yamakawa, Kumiko Iijima, Kaoru Mogushi, Hiroshi Tanaka, Keizo Sato, Hidekazu Suzuki, Tohru Mizushima
JournalNature communications (Nat Commun) Vol. 4 Pg. 2686 ( 2013) ISSN: 2041-1723 [Electronic] England
PMID24189798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anions
  • Anti-Inflammatory Agents
  • Benzilates
  • Bronchodilator Agents
  • NF-kappa B
  • Piperidines
  • Superoxides
  • mepenzolic acid
  • NADPH Oxidase
  • Pancreatic Elastase
Topics
  • 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, physiopathology)
  • Male
  • Mice
  • Mice, Inbred DBA
  • Mice, Inbred ICR
  • NADPH Oxidase (metabolism)
  • NF-kappa B (metabolism)
  • Pancreatic Elastase (adverse effects, antagonists & inhibitors)
  • Piperidines (pharmacology)
  • Pulmonary Disease, Chronic Obstructive (drug therapy)
  • Pulmonary Emphysema (drug therapy)
  • Superoxides (chemistry)
  • Swine
  • Time Factors

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