YM-40461, a Potent Surfactant Secretagogue, Improves Mucociliary Clearance in SO₂-Exposed Guinea Pigs

抄録

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 gh 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.