THE EFFECTS OF YM26818 - 1-(2-DIMETHYLAMI NOETHYL)-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 surfacta nt (PS) secretion, we studied the effects of various compounds on PS s ecretion by measuring the contents of PS in the bronchoalveolar lavage (BAL) fluid in guinea pigs. In the chemical modification study of amb roxol, which is known as a PS secretagogue, and a compound we discover ed from our compounds library, imethylaminoethyl)-1-(3,4,5-trimethoxyp henyl)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 gui nea 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). Concomitant ly by these effects, the recovery of lung compliance was observed in t his model (A UC 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 i ndicate that YM-26818 is useful for the therapy of adult respiratory d istress syndrome (ARDS) and obstructive pulmonary diseases.