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 language | English |
|---|---|
| Article number | 2686 |
| Journal | Nature Communications |
| Volume | 4 |
| DOIs | |
| Publication status | Published - 2013 Nov 5 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease
AU - Tanaka, Ken Ichiro
AU - Ishihara, Tomoaki
AU - Sugizaki, Toshifumi
AU - Kobayashi, Daisuke
AU - Yamashita, Yasunobu
AU - Tahara, Kayoko
AU - Yamakawa, Naoki
AU - Iijima, Kumiko
AU - Mogushi, Kaoru
AU - Tanaka, Hiroshi
AU - Sato, Keizo
AU - Suzuki, Hidekazu
AU - Mizushima, Tohru
PY - 2013/11/5
Y1 - 2013/11/5
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms3686
DO - 10.1038/ncomms3686
M3 - Article
C2 - 24189798
AN - SCOPUS:84889250123
VL - 4
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2686
ER -