YM-40461 improves airway clearance in guinea pigs with induced subacute bronchitis.

Abstract	The effects of the surfactant secretagogue YM-40461 on the mucociliary transport (MCT) velocity were examined in guinea pigs with induced bronchitis. Guinea pigs were exposed to SO2 gas (900 ppm, 3 h/d) for 5 d. MCT velocity was measured by the movement of a 30% gelatin solution containing Evans blue dye placed on the tracheal mucosal surface. Repeated doses of YM-40461 improved the MCT guinea pigs with bronchitis within 5 d after the completion of SO2 exposure, with an ED50 value of 3.1 mg/kg p.o. At a dose of 10 mg/kg p.o., YM-40461 restored MCT to the control level (98.0% recovery). Ambroxol, bromhexine and salbutamol also improved MCT, but were far less effective than YM-40461. Airway fluid collected from bronchitic animals revealed increased disaturated phosphatidylcholine (DSPC, a major component of surfactants)-to-protein ratio and decreased surface tension produced by YM-40461 treatment (10 mg/kg). These results suggest that YM-40461 ameliorates MCT dysfunction in animals with SO2 gas-induced bronchitis by increasing the DSPC-to-protein ratio in the airway.
Authors	A Kimoto, Y Hirano, T Iwai, M Saitou, K Tomioka, K Miyata, T Yamada
Journal	Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 23 Issue 12 Pg. 1441-4 (Dec 2000) ISSN: 0918-6158 [Print] Japan
PMID	11145174 (Publication Type: Journal Article)
Chemical References	Phenylurea Compounds Phosphatidylcholines Proteins Pulmonary Surfactants YM 26818 lecithins, disaturated Sulfur Dioxide
Topics	Animals Bronchitis (chemically induced, drug therapy, physiopathology) Chronic Disease Dose-Response Relationship, Drug Guinea Pigs Male Mucociliary Clearance (drug effects, physiology) Phenylurea Compounds (pharmacology) Phosphatidylcholines (metabolism) Proteins (metabolism) Pulmonary Surfactants (metabolism) Secretory Rate (drug effects) Sulfur Dioxide Surface Tension (drug effects) Trachea (drug effects, metabolism)

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