Aishi Kimoto, Munetoshi Saito, Yasuno Hirano, Takaya Iwai, Kenichi Tomioka,
Keiji Miyata and Toshimitsu Yamada
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.,
Ltd., 21 Miyukigaoka, Tsukuba-city, Ibaraki 305-8585, Japan
Abstract: 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ﾊppm for
3ﾊh). MCT velocity was measured by means of the dye gelatin technique. YM-40461
at doses of 1-10ﾊmg/kg, p.o. induced recovery of MCT function, with an ED50
value of 2.4ﾊmg/kg. Maximal recovery (78.0ﾊｱﾊ12.5%)
was observed 2ﾊh in the animals treated with 10ﾊmg/kg of YM-40461. Ambroxol
and bromhexine showed less effect on the MCT dysfunction than YM-40461.
An artificial surfactant (Surfactenｨ) also aided recovery. YM-40461
at a dose of 10ﾊ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.
Keywords: Surfactant secretagogue, Mucociliary transport, Bronchitis