Superiority of pulmonary administration of mepenzolate bromide over other routes as treatment for chronic obstructive pulmonary disease

Ken Ichiro Tanaka, Shota Kurotsu, Teita Asano, Naoki Yamakawa, Daisuke Kobayashi, Yasunobu Yamashita, Hiroshi Yamazaki, Tomoaki Ishihara, Hiroshi Watanabe, Toru Maruyama, Hidekazu Suzuki, Tohru Mizushima

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Abstract

We recently proposed that mepenzolate bromide (mepenzolate) would be therapeutically effective against chronic obstructive pulmonary disease (COPD) due to its both anti-inflammatory and bronchodilatory activities. In this study, we examined the benefits and adverse effects associated with different routes of mepenzolate administration in mice. Oral administration of mepenzolate caused not only bronchodilation but also decreased the severity of elastase-induced pulmonary emphysema; however, compared with the intratracheal route of administration, about 5000 times higher dose was required to achieve this effect. Intravenously or intrarectally administered mepenzolate also showed these pharmacological effects. The intratracheal route of mepenzolate administration, but not other routes, resulted in protective effects against elastase-induced pulmonary damage and bronchodilation at a much lower dose than that which affected defecation and heart rate. These results suggest that the pulmonary route of mepenzolate administration may be superior to other routes (oral, intravenous or intrarectal) to treat COPD patients.

Original languageEnglish
Article number04510
JournalScientific reports
Volume4
DOIs
Publication statusPublished - 2014 Mar 28

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Tanaka, K. I., Kurotsu, S., Asano, T., Yamakawa, N., Kobayashi, D., Yamashita, Y., Yamazaki, H., Ishihara, T., Watanabe, H., Maruyama, T., Suzuki, H., & Mizushima, T. (2014). Superiority of pulmonary administration of mepenzolate bromide over other routes as treatment for chronic obstructive pulmonary disease. Scientific reports, 4, [04510]. https://doi.org/10.1038/srep04510