SELECTIVE BLOCKADE OF CHOLECYSTOKININ TYPE-B RECEPTORS WITH L-365,260DOES NOT IMPAIR GALLBLADDER CONTRACTION IN NORMAL HUMANS

Objectives: To evaluate the effect of selective blockade of type B cho lecystokinin receptors on gall bladder contraction in normal humans an d to compare methods for quantitative analysis of gall bladder contrac tion. Methods: L-365,260, a novel, nonpeptide cholecystokinin antagoni st shown to be selective for type B cholecystokinin receptors, was adm inistered every 6 h over a 5-7-day period. Plasma levels of L-365,260 were determined by high pressure liquid chromatography. Gallbladder co ntraction after a standardized fatty meal was measured by ultrasonogra phy, and results were calculated by ellipsoid or sum of cylinders meth ods. Results: L-365,260 levels were comparable to levels in earlier st udies demonstrating inhibition of pentagastrin-stimulated acid secreti on in normal subjects and blockade of anxiogenic effects of cholecysto kinin injections in patients with panic disorder. Regardless of the me thod used for estimating gallbladder size, none of the L-365,260 doses studied inhibited gallbladder contraction. Gallbladder size was most consistently estimated by the ellipsoid method using measurements norm alized to individual values for minimum and maximum gallbladder dimens ions. Conclusions: Multiple oral doses of L-365,260 do not alter ultra sonographically assessed gallbladder contraction at doses shown to be clinically effective in earlier studies. Despite being more difficult to implement, the sum of cylinders method for estimating gall bladder size offers no advantage over the ellipsoid method.