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Am J Physiol Regul Integr Comp Physiol 280: R1149-R1154, 2001;
0363-6119/01 $5.00
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Vol. 280, Issue 4, R1149-R1154, April 2001

Loxiglumide, a CCK-A receptor antagonist, stimulates calorie intake and hunger feelings in humans

Christoph Beglinger1,2, Lukas Degen1, Daniel Matzinger1,2, Massimo D'Amato4, and Jürgen Drewe1,3

1 Department of Research, 2 Division of Gastroenterology, and 3 Division of Clinical Pharmacology, University Hospital, CH-4031 Basel, Switzerland; and 4 Rotta Research Laboratorium, I-20052 Monza, Italy

Exogenous cholecystokinin (CCK) induces early satiety when infused into humans. Whether alimentary CCK (CCK-A) receptor blockade stimulates food intake in humans is, however, uncertain. The aim of the present investigation was, therefore, to establish the effect of CCK-A receptor blockade on satiety and eating behavior in healthy volunteers. To further explore the role of endogenous CCK, the effects of the specific CCK-A receptor antagonist loxiglumide (Lox; 22 µmol · kg-1 · h-1) on satiety and eating behavior were investigated in healthy men and compared with saline infusions (as placebo) in a series of randomized, double-blind, placebo-controlled, crossover studies. Lox produced a slight (7%), but not significant (P = 0.104), increase in food intake that was accompanied by a modest (10%), but significant (P < 0.004), increase in calorie intake. Fluid ingestion was not affected by Lox. Subjects experienced more hunger and delayed fullness during Lox infusion than during saline infusion (P < 0.05). This study provides further evidence that CCK is an endogenous physiological satiety signal acting through CCK-A receptor-mediated mechanisms. Repeated-dose studies comparing hunger and satiety responses after CCK-A receptor blockade in healthy subjects and patients with eating disorders may help clarify the possible involvement of endogenous CCK in these conditions.

cholecystokinin; appetite; eating behavior


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