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 (400Êppm for 3Êh). MCT velocity was measured by means of the dye gelatin technique. YM-40461 at doses of 1-10Êmg/kg, p.o. induced recovery of MCT function, with an ED50 value of 2.4Êmg/kg. Maximal recovery (78.0Ê±Ê12.5%) was observed 2Êh in the animals treated with 10Êmg/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 10Êmg/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