Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying

When administered exogenously, the gastrointestinal peptide hormone cholecystokinin (CCK) has a number of physiological effects, including inhibition of gastric emptying and increased gallbladder contraction. The extent to which these functions are affected by CCK that is released by the body (endogenous) is not known. Studies in man using compounds that block the actions of CCK (antagonists), which would provide information on the effects of endogenous CCK, have been hampered by the short duration of action and poor potency of CCK antagonists currently available. A study was carried out in 10 healthy volunteers (five male, five female; 25 to 41 years of age) using a safe, potent CCK antagonist, loxiglumide. Following a 12-hour fast, either two 400 mg tablets of loxiglumide or two placebo tablets were given. Subjects then consumed a standard liquid-solid meal of common foods, and gallbladder contractions and gastric emptying were monitored at intervals up to 300 minutes using ultrasonography. Gallbladder contractions were inhibited by approximately 75 percent following loxiglumide administration compared with placebo; no differences were seen in the rate of gastric emptying between the two groups at any time point. These results differ from previous experiments where exogenous CCK administration affected both gastric emptying and gallbladder contraction, and indicate that endogenous CCK released in response to a meal affects only gallbladder contraction in man. (Consumer Summary produced by Reliance Medical Information, Inc.)