YM-40461, a potent surfactant secretagogue, improves mucociliary clearance in SO2-exposed guinea pigs.
The effects of the new pulmonary surfactant secretagogue YM-40461, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl) urea, on tracheal mucociliary transport (MCT) were assessed using guinea pigs with acute bronchitis. Acute bronchitis was induced by SO2 gas exposure (400 ppm for 3 h). MCT velocity was measured by means of the dye gelatin technique. YM-40461 at doses of 1-10 mg/kg, p.o. induced recovery of MCT function, with an ED50 value of 2.4 mg/kg. Maximal recovery (78.0+/-12.5%) was observed 2 h in the animals treated with 10 mg/kg of YM-40461. Ambroxol and bromhexine showed less effect on the MCT dysfunction than YM-40461. An artificial surfactant (Surfacten) also aided recovery. YM-40461 at a dose of 10 mg/kg, p.o. significantly improved surfactant production without affecting mucus secretion. These results show that YM-40461 ameliorates MCT dysfunction caused by SO2 exposure by activation of pulmonary surfactant secretion.
Kimoto
A
A
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba-city, Ibaraki, Japan.
Saito
M
M
Hirano
Y
Y
Iwai
T
T
Tomioka
K
K
Miyata
K
K
Yamada
T
T
D000818:Animals; D001988:Bronchiolitis / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D005643:Fucose / Q000378:metabolism; D008297:Male; D051379:Mice; D009079:Mucociliary Clearance / Q000187:drug effects*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D013458:Sulfur Dioxide / Q000494:pharmacology*
D010671:Phenylurea Compounds; D011663:Pulmonary Surfactants; C114914:YM 26818; D013458:Sulfur Dioxide; D005643:Fucose