Abstract
Background: Cannabinoid type 1 (CB1) receptors have been implicated in the control of transient lower esophageal sphincter (LES) relaxations (TLESRs) in animals. In man, nonscpecific cannabinoid receptor agonism was found to inhibit TLESRS, but it is unclear whether CB1 receptors are involved in the control of esophageal function. Aim: To study the effects of the CB1 receptor antagonist rimonabant on fasting and postprandial LES function in healthy subjects. Methods: Eleven healthy volunteers underwent two esophageal sleeve manometry studies after 3 days premedication with placebo or rimonabant 20 mg/ day. Drug was administered after 30 minutes and a standardized meal was administered after 90 minutes, with measurements continuing to 120 minutes postprandially. Throughout the study, 10 wet swallows were administered at 30-minute intervals. Results: Intragastric pressure was significantly enhanced by pretreatment with rimonabant (24.5±1.5 vs. 20.4±1.7 mmHg, p=0.01). Rimonabant did not significantly alter preprandial LES pressure (20.3±4.0 vs. 17.3±3.0 mmHg, NS), but postprandial LES pressures were significantly enhanced (ANOVA p<0.01), with post-hoc significant differences at 30, 60, 90, and 120 minutes after the end of the meal (respectively 17.1±2.7 vs. 10.0±1.7; 17.8±3.3 vs. 10.2±1.6; 19.3±3.6 vs. 10.4±1.3 mmHg and 19.6±3.1 vs. 8.6±3.0; all p<0.05). Swallow-induced relaxations (97±1 vs. 97±1%, NS) and amplitude of peristaltic contractions were not altered, but rimonabant significantly increased the duration of peristaltic contraction waves at all time points (e.g. 5.0±0.3 vs. 8.0±0.3 sec preprandially and 5.0±0.2 vs. 8.2±0.3 sec at 30 min postprandially, both p<0.01). The tendency of a decreased number of TLESRs after rimonabant did not reach statistical significance (TLESRs total 2.3±0.8 vs. 3.3±0.5, p=0.08; preprandially 0.6±0.2 vs.1.3±0.3, p=0.14; postprandially 1.6±0.8 vs. 2.0±0.4, p=0.10). Conclusion: The CB1 receptor antagonist rimonabant enhances postprandial LES pressure and tends to decrease TLESRs in healthy subjects.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
