Effect of YM-40461, a novel surfactant secretagogue, on chronic obstructive pulmonary diseases and similar symptoms in guinea pigs.

Abstract

YM-40461 (1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea, CAS 142912-85-4), is a novel surfactant secretagogue. The effect of YM-40461 on symptoms, e.g. change of airway functions and hypoxemia, were examined using guinea pigs with induced subacute bronchitis. Bronchitic guinea pigs exhibited basal lung resistance (RL) was 0.152 +/- 0.005 cm H2O/ml/s (normal: 0.130 +/- 0.002 cm H2O/ml/s) and basal lung compliance (CL) of 0.455 +/- 0.011 ml/cm H2O (normal: 0.509 +/- 0.009 ml/cm H2O). Although YM-40461 slightly improved the lung resistance in these animals, it improved significantly and dose-dependently the lung compliance (0.468 +/- 0.008 ml/cm H2O for 1 mg/kg, 0.477 +/- 0.008 for 3 mg/kg, 0.490 +/- 0.011 for 10 mg/kg, p < 0.05 at 10 mg/kg) compared to nontreated bronchitic guinea pigs. YM-40461 improved airway functions in bronchitic guinea pigs just as wall as the beta 2-adrenoceptor agonist salbutamol. Additionally, YM-40461 significantly reduced airway hyperreactivity in response to intravenously infused acetylcholine (ACh). Basal PaO2 was 83.1 +/- 0.7 cm H2O in healthy guinea pigs and 71.2 +/- 1.7 cm H2O in bronchitic guinea pigs, indicating hypoxemia. A dose of 10 mg/kg of YM-40461 relieved hypoxemia in these animals with the values returning to 81.8 +/- 1.9 cm H2O (p < 0.05). These results suggest that YM-40461 ameliorates chronic obstructive pulmonary disease (COPD)-like symptoms in bronchitis models due to increased surfactant in the airway.

• Authors: A Kimoto, M Saito, Y Hirano, T Iwai, T Yamada, K Miyata
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 51 Issue 9 Pg. 743-7 (Sep 2001) ISSN: 0004-4172 [Print] Germany
• PMID: 11642007 (Publication Type: Journal Article)

Chemical References

• Phenylurea Compounds
• Surface-Active Agents
• YM 26818
• Sulfur Dioxide
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Animals
• Blood Gas Analysis
• Bronchial Hyperreactivity (chemically induced, prevention & control)
• Bronchitis (chemically induced, prevention & control)
• Guinea Pigs
• Hypoxia (chemically induced, prevention & control)
• Male
• Phenylurea Compounds (therapeutic use)
• Pulmonary Disease, Chronic Obstructive (chemically induced, drug therapy)
• Respiratory Function Tests
• Sulfur Dioxide
• Surface-Active Agents (therapeutic use)