Influence of tegaserod on proximal gastric tone and on the perception of gastric distention in functional dyspepsia.
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.


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
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.
Tack
J
J
Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium. jan.tack@med.kuleuven.ac.be
Janssen
P
P
Bisschops
R
R
Vos
R
R
Phillips
T
T
Tougas
G
G
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004415:Dyspepsia / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D019518:Postprandial Period / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D013270:Stomach / Q000187:drug effects* / Q000503:physiopathology; D016896:Treatment Outcome
D007211:Indoles; D017366:Serotonin Receptor Agonists; C105050:tegaserod