title: Superiority of pulmonary administration of mepenzolate bromide over other routes as treatment for chronic obstructive pulmonary disease.
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.
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Kurotsu
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Teita
authors.initials: T
authors.lastname: Asano
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamakawa
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ishihara
authors.affiliation: Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001561:Benzilates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D016903:Drug Monitoring; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride / Q000009:adverse effects; D051379:Mice; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D001561:Benzilates; D010880:Piperidines; D016210:Methacholine Chloride; C005101:mepenzolic acid