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, Tohru Mizushima

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Article number2686
JournalNature Communications
Volume4
DOIs
Publication statusPublished - 2013 Nov 5

Fingerprint

Pulmonary diseases
Pancreatic Elastase
airspace
Chronic Obstructive Pulmonary Disease
mice
bromides
Muscarinic Antagonists
emphysema
Inhalation Administration
disorders
Lung
inorganic peroxides
smoke
Emphysema
respiration
Smoke
Tobacco Products
Superoxides
Libraries
drugs

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Tanaka, K. I., Ishihara, T., Sugizaki, T., Kobayashi, D., Yamashita, Y., Tahara, K., ... Mizushima, T. (2013). Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease. Nature Communications, 4, [2686]. https://doi.org/10.1038/ncomms3686

Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease. / Tanaka, Ken Ichiro; Ishihara, Tomoaki; Sugizaki, Toshifumi; Kobayashi, Daisuke; Yamashita, Yasunobu; Tahara, Kayoko; Yamakawa, Naoki; Iijima, Kumiko; Mogushi, Kaoru; Tanaka, Hiroshi; Sato, Keizo; Suzuki, Hidekazu; Mizushima, Tohru.

In: Nature Communications, Vol. 4, 2686, 05.11.2013.

Research output: Contribution to journalArticle

Tanaka, KI, Ishihara, T, Sugizaki, T, Kobayashi, D, Yamashita, Y, Tahara, K, Yamakawa, N, Iijima, K, Mogushi, K, Tanaka, H, Sato, K, Suzuki, H & Mizushima, T 2013, 'Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease', Nature Communications, vol. 4, 2686. https://doi.org/10.1038/ncomms3686
Tanaka, Ken Ichiro ; Ishihara, Tomoaki ; Sugizaki, Toshifumi ; Kobayashi, Daisuke ; Yamashita, Yasunobu ; Tahara, Kayoko ; Yamakawa, Naoki ; Iijima, Kumiko ; Mogushi, Kaoru ; Tanaka, Hiroshi ; Sato, Keizo ; Suzuki, Hidekazu ; Mizushima, Tohru. / Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease. In: Nature Communications. 2013 ; Vol. 4.
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