Cholecystokinin antagonistic activities of loxiglumide.

Cholecystokinin (CCK) antagonistic activities of loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-pentylgl utaramic acid, CR1505, CAS 107097-80-3) were investigated in the gastrointestine and gallbladder in vivo. Intravenous administration of loxiglumide antagonized the CCK-induced reduction of gastric emptying in rats, acceleration of intestinal transport in mice, increase in ileal motility in rabbits, gallbladder contraction in guinea pigs and acceleration of gallbladder emptying in mice. Orally administered loxiglumide also antagonized the CCK-induced gallbladder emptying in mice. Furthermore, egg yolk-stimulated gallbladder emptying in mice was also inhibited by loxiglumide, indicating that this agent antagonizes not only exogenous but also endogenous CCK. These results demonstrate that loxiglumide is an intravenously and orally effective, potent CCK antagonist.