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.