SR 48692, a specific neurotensin receptor antagonist, has no effect on oesophageal motility in humans

Background: The administration of exogenous neurotensin can reduce the lower oesophageal sphincter pressure, but it is unclear whether this effect is pharmacological or physiological. Aim: A specific neurotensin receptor antagonist (SR 48692) was used to assess the effect of endogenous neurotensin on lower oesophageal sphincter function. Methods: Twenty-four healthy male subjects were included in a double-blind, placebo-controlled, randomized, cross-over study designed to determine the effects of two single doses (90 and 300 mg, preceded by a loading dose) of SR 48692 on the resting lower oesophageal sphincter pressure, transient lower oesophageal sphincter relaxations, primary oesophageal peristalsis and oesophageal acid exposure. Oesophageal pH and motility recordings were performed during 1 h of fasting and 3 h post-prandially. Plasma neurotensin-like immunoreactivity release was determined by radioimmunoassay. Results: During fasting, the lower oesophageal sphincter pressure, transient lower oesophageal sphincter relaxation rate and reflux episodes were similar with the two doses of SR 48692 and placebo. Meal ingestion induced a rise in plasma neurotensin-like immunoreactivity, a decrease in lower oesophageal sphincter pressure and an increase in both the transient lower oesophageal sphincter relaxation rate and the number of reflux episodes, which were not significantly modified by SR 48692. SR 48692 did not affect oesophageal primary peristalsis. Conclusion: This study shows that SR 48692, a specific neurotensin 1 receptor antagonist, has no effect on oesophageal motility in humans.