Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease

Ken-Ichiro Tanaka, Tomoaki Ishihara, Toshifumi Sugizaki, Daisuke Kobayashi, Yasunobu Yamashita, Kayoko Tahara, Naoki Yamakawa, Kumiko Iijima, Kaoru Mogushi, Hiroshi Tanaka, Keizo Sato, Hidekazu Suzuki and Tohru Mizushima ()
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Ken-Ichiro Tanaka: Faculty of Pharmacy, Keio University
Tomoaki Ishihara: Faculty of Pharmacy, Keio University
Toshifumi Sugizaki: Faculty of Pharmacy, Keio University
Daisuke Kobayashi: Faculty of Pharmacy, Keio University
Yasunobu Yamashita: Faculty of Pharmacy, Keio University
Kayoko Tahara: Faculty of Pharmacy, Keio University
Naoki Yamakawa: Faculty of Pharmacy, Keio University
Kumiko Iijima: Medical Research Institute, Tokyo Medical and Dental University
Kaoru Mogushi: Medical Research Institute, Tokyo Medical and Dental University
Hiroshi Tanaka: Medical Research Institute, Tokyo Medical and Dental University
Keizo Sato: Kyushu University of Health and Welfare
Hidekazu Suzuki: Keio University School of Medicine
Tohru Mizushima: Faculty of Pharmacy, Keio University

Nature Communications, 2013, vol. 4, issue 1, 1-13

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3686

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