Influence of tegaserod on proximal gastric tone and on the perception of gastric distention in functional dyspepsia.
Author(s): Tack J, Janssen P, Bisschops R, Vos R, Phillips T, Tougas G
Affiliation(s): Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium. jan.tack@med.kuleuven.ac.be
Publication date & source: 2011-02, Neurogastroenterol Motil., 23(2):e32-9. Epub 2010 Oct 27.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
BACKGROUND: Abnormalities in gastric sensorimotor function (hypersensitivity to distention and impaired meal accommodation) have been implicated in the pathophysiology of functional dyspepsia (FD). To study the effect of the 5-HT(4) agonist tegaserod on sensitivity to gastric distention and gastric accommodation in FD. METHODS: Thirty FD patients (7 males, mean age 42 +/- 2 years) underwent a gastric barostat study on two separate occasions, 2 weeks apart, after 5 days of pretreatment with placebo or tegaserod 6 mg b.i.d. in a double-blind randomized order. After introduction of the barostat bag, graded isobaric distentions (2 mmHg increments/2 min) were performed to determine gastric compliance and sensitivity to distention. Subsequently, the pressure level was set at intra-abdominal pressure [minimal distending pressure (MDP)] + 2 mmHg for 90 min, with administration of a liquid meal (200 mL; 300 kcal) after 30 min. KEY RESULTS: Tegaserod had no influence on MDP (7.9 +/- 0.4 vs 7.4 +/- 0.4 mmHg) or fasting gastric compliance (44 +/- 10 vs 61 +/- 6 mL mmHg(-1)) and on fasting thresholds for first perception (3.6 +/- 0.4 vs 4.2 +/- 0.2 mmHg above MDP) or discomfort (9.9 +/- 0.7 vs 10.5 +/- 0.5 mmHg above MDP). Tegaserod did not alter intra-balloon volumes before and after the meal [respectively 146 +/- 14 vs 120 +/- 11 and 297 +/- 28 vs 283 +/- 29 mL, not significant (NS)], or the amplitude of the meal-induced gastric relaxation (151 +/- 23 vs 162 +/- 23 mL, NS). In the subgroup with normal gastric emptying (n = 22), tegaserod significantly enhanced meal-induced accommodation (126 +/- 23 vs 175 +/- 29 mL, ANOVA P < 0.001). CONCLUSIONS & INFERENCES: Tegaserod does not alter gastric sensorimotor function in FD patients as a group. In the subgroup with normal gastric emptying, tegaserod 6 mg b.i.d enhanced gastric accommodation. (c) 2010 Blackwell Publishing Ltd.
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