The Effect of Oral Buspirone, Pyridostigmine, and Bethanechol on Esophageal Function Evaluated With Combined Multichannel Esophageal Impedance-manometry in Healthy Volunteers

Background: There is limited information on medications with promotility effects on the esophagus. Studies in healthy volunteers have shown the potential role of the direct cholinergic agonist bethanechol and the serotonin receptor agonist buspirone in improving esophageal motility. It has been also shown that an acetylcholinesterase inhibitor, the short-acting drug edrophonium administered intravenously caused a greater increase in the esophageal contraction amplitude and duration than bethanechol. Edrophonium cannot be used as a promotility therapy owing to short duration of action and lack of oral administration. The use of another acetylcholinesterase inhibitor pyridostygmine with longer duration of action has not been studied. The aim of the Study was to evaluate the effect of oral pyridostygmine (60 mg), buspirone (20 mg), and bethanechol (25 mg) on esophageal function assessed by combined multichannel intraluminal impedance-esophageal manometry. Materials and Methods: Ten healthy volunteers were enrolled in a double blind randomized 3-period crossover study. Multichannel intraluminal impedance-esophageal manometry recorded esophageal pressures and bolus transit data during 6 liquid and 6 viscous swallows at baseline and 20, 40, and 60 minutes after the randomized oral administration of each drug. Results: Blinded analysis found significant increases in mean distal esophageal amplitude for liquid swallows from baseline to 60 Minutes postdosing after pyridostygmine (87.6 vs. 118.0 mm Hg, P < 0.001), buspirone (85.1 vs. 101.9 mm Hg, P<0.05), and bethanechol (87.6 vs. 118.8 mm Hg, P < 0.01). Only pyriclostygmine showed a significant decrease in mean distal onset velocity for liquid swallows at 60 minutes postdosing (3.4 vs. 2.3cm/s, P < 0.01) and increase in total bolus transit time at 60 Minutes postdosing (7.9 vs. 9.3 s, P<0.05). All 3 agents significantly increased mean lower esophageal sphincter residual pressure for liquid swallows at 20, 40, and 60 Minutes postdosing. Increased lower esophageal sphincter resting pressure was not significant. Similar results were found with viscous swallows. Conclusions: Oral pyridostygmine, buspirone, and bethanechol enhance esophageal motility with pyridostygmine appearing to have the greatest effect. A potential effect on improving esophageal function and symptoms in patients requires further study.