Effect of loxiglumide on gallbladder contractile response to cerulein and food in humans.
The present study investigated the effect of loxiglumide, a new selective cholecystokinin-receptor antagonist, on the gallbladder contractile responses to caerulein and to food in humans. In 6 healthy men, the gallbladder emptying driven by intravenous infusion of stepwise increasing doses of cerulein (10-80 ng/kg . h) and that induced by a 550-cal standard meal were monitored by ultrasonography. In both sets of experiments, the effect of loxiglumide was tested at various infusional rates against a control infusion of saline. An infusional rate of 2.5 mg/kg . h of loxiglumide abolished the gallbladder response even to maximal doses of cerulein, whereas a rate of 1.0 mg/kg . h counteracted the cholecystokinetic activity of cerulein up to the dose of 20 ng/kg . h. In postprandial experiments, the cholecystokinin antagonist dose-dependently inhibited the physiologic gallbladder contraction. The maximal gallbladder emptying, which always occurred 85 min after the meal, was 71.1% +/- 3.3% of basal volume in control studies, 39.2% +/- 1.8% during infusion of 2.5 mg/kg . h of loxiglumide, and 17.3% +/- 5.9% when 5.0 mg/kg . h were infused. A dose of 7.5 mg/kg . h of loxiglumide was able to prevent any postprandial emptying of the gallbladder. The present study shows that a selective cholecystokinin receptorial blockade competitively antagonizes cerulein-induced gallbladder contraction and dose-dependently inhibits postprandial gallbladder emptying.
Malesci
A
A
Istituto di Medicina Interna, Università di Milano, Italy.
De Fazio
C
C
Festorazzi
S
S
Bonato
C
C
Valentini
A
A
Tacconi
M
M
Rovati
L
L
Setnikar
I
I
D000328:Adult; D002108:Ceruletide / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D005973:Glutamine / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors
D005973:Glutamine; C053737:loxiglumide; D002108:Ceruletide; D002766:Cholecystokinin; D011377:Proglumide