Biliary spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) in dogs

The spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) on the biliary tract was investigated in anesthetized dogs. Intravenous administration of AA-149 at 2 mg/kg and higher doses produced a dose-dependent reduction in passage resistance through the choledochoduodenal junction and in gallbladder pressure, and a dose-dependent increase in bile flow. AA-149, like cholecystokinin, decreased biliary ductal pressure in spite of increasing the bile flow in dogs with ligation of the cystic duct of the gallbladder, whereas taurocholate increased the pressure as well as the bile flow. Moreover, the spasmic response of the choledochoduodenal junction to morphine was depressed strongly by AA-149, BUT NOT CONSISTENTLY BY ATROPINE. The effects of AA-149 were not influenced by pretreatment with atropine, phentolamine or propranolol. These findings strongly suggest that AA-149 relaxed the biliary tract and depressed the morphine-induced spasm by a mechanism different from those of anticholinergic and sympathomimetic agents.