Effect of rimonabant on oesophageal motor function in man

BACKGROUND: Cannabinoid type 1 (CB1) receptors are implicated in the control of transient lower oesophageal sphincter relaxations (TLESRs) in animals. In man, it is unclear whether CB1 receptors are involved in the control of oesophageal function. AIM: To study the effects of the CB1 receptor antagonist rimonabant on fasting and postprandial LES function in healthy subjects. METHODS: Twelve healthy volunteers underwent two oesophageal manometry studies with administration of wet swallows and a meal after 3 days' premedication with placebo or rimonabant 20 mg. RESULTS: Rimonabant did not significantly alter preprandial LES pressure (21.1±4.0 vs. 17.3±3.0 mmHg, N.S.), but postprandial LES pressures were significantly enhanced (9.9±1.9 vs.17.1±2.7 mmHg in the first and 10.0±1.4 vs. 19.3±3.6 mmHg in the second postprandial hour, both P<0.05). Swallow-induced relaxations and amplitude of peristaltic contractions were not altered, but rimonabant significantly increased the duration of peristaltic contractions at all time points (e.g. 5.0±0.3 vs. 8.0±0.3s preprandially and 5.0±0.2 vs. 8.2±0.3s at 60 min postprandially, both P<0.01). The number of postprandial TLESRs (3.1±0.5 vs. 1.2±0.5, P<0.05) and acid reflux episodes (1.4±0.2 vs. 0.3±0.1, P<0.05) were significantly lower after rimonabant. CONCLUSION: The CB1 receptor antagonist rimonabant enhances postprandial LES pressure and decreases TLESRs in healthy subjects.