[The effects of YM26818: 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea and derivatives on pulmonary surfactant secretion and lung compliance].
To discover a novel compound which has an effect on pulmonary surfactant (PS) secretion, we studied the effects of various compounds on PS secretion by measuring the contents of PS in the bronchoalveolar lavage (BAL) fluid in guinea pigs. In the chemical modification study of ambroxol, which is known as a PS secretagogue, and a compound we discovered from our compounds library, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea: YM-26818 (the increasing effect on PS in BALF, 34.7% at 50 mg/kg, i.p.). In the surfactant deficient model induced by BAL in guinea pigs, YM-26818 (5 and 10 mg/kg, p.o.) significantly increased the contents of PS in the BAL fluid compared with that of control animals (5 mg/kg: 60.3 +/- 8.0, 10 mg/kg: 59.4 +/- 4.3% increase). Concomitantly by these effects, the recovery of lung compliance was observed in this model (AUC of lung volume, control: 560 +/- 15, YM-26818 5 mg/kg: 898 +/- 51, YM-2681 10 mg/kg: 956 +/- 11 ml.min). These results may indicate that YM-26818 is useful for the therapy of adult respiratory distress syndrome (ARDS) and obstructive pulmonary diseases.
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
A
A
Kimoto
M
M
Saito
Y
Y
Hirano
T
T
Iwai
K
K
Tomioka
K
K
Miyata
T
T
Yamada
T
T
Maruyama
N
N
Imanishi
H
H
Hara
T
T
Mase
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006168:Guinea Pigs; D008170:Lung Compliance / Q000187:drug effects*; D008297:Male; D010671:Phenylurea Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010743:Phospholipids / Q000032:analysis; D011663:Pulmonary Surfactants / Q000032:analysis / Q000378:metabolism*; D013268:Stimulation, Chemical
D010671:Phenylurea Compounds; D010743:Phospholipids; D011663:Pulmonary Surfactants; C114914:YM 26818