Blonski Wojciech, Vela Marcelo F, Freeman Janice, Sharma Neeraj, Castell Donald O
Division of Gastroenterology, Medical University of South Carolina, Charleston, SC 29425, USA.
J Clin Gastroenterol. 2009 Mar;43(3):253-60. doi: 10.1097/MCG.0b013e318167b89d.
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.
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.
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 pyridostygmine showed a significant decrease in mean distal onset velocity for liquid swallows at 60 minutes postdosing (3.4 vs. 2.3 cm/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.
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.
关于对食管有促动力作用的药物的信息有限。在健康志愿者中进行的研究表明，直接胆碱能激动剂氯贝胆碱和5-羟色胺受体激动剂丁螺环酮在改善食管动力方面具有潜在作用。还表明，一种乙酰胆碱酯酶抑制剂，即静脉注射的短效药物依酚氯铵，比氯贝胆碱能使食管收缩幅度和持续时间有更大的增加。由于作用持续时间短且缺乏口服剂型，依酚氯铵不能用作促动力治疗药物。另一种作用持续时间较长的乙酰胆碱酯酶抑制剂吡啶斯的明的应用尚未得到研究。本研究的目的是通过联合多通道腔内阻抗-食管测压法评估口服吡啶斯的明（60毫克）、丁螺环酮（20毫克）和氯贝胆碱（25毫克）对食管功能的影响。
10名健康志愿者参加了一项双盲随机3期交叉研究。多通道腔内阻抗-食管测压法记录了在基线时以及随机口服每种药物后20、40和60分钟时6次液体吞咽和6次黏稠吞咽过程中的食管压力和团块通过数据。
盲法分析发现，吡啶斯的明给药后60分钟，液体吞咽时平均食管远端收缩幅度从基线显著增加（87.6对118.0毫米汞柱，P<0.001），丁螺环酮（85.1对101.9毫米汞柱，P<0.05），氯贝胆碱（87.6对118.8毫米汞柱，P<0.01）。只有吡啶斯的明在给药后60分钟时显示液体吞咽的平均食管远端起始速度显著降低（3.4对2.3厘米/秒，P<0.01），给药后60分钟时总团块通过时间增加（7.9对9.3秒，P<0.05）。所有3种药物在给药后20、40和60分钟时均使液体吞咽的平均食管下括约肌残余压力显著增加。食管下括约肌静息压力增加不显著。黏稠吞咽也得到了类似结果。
口服吡啶斯的明、丁螺环酮和氯贝胆碱可增强食管动力，其中吡啶斯的明似乎作用最大。对改善患者食管功能和症状的潜在作用需要进一步研究。
