Delvaux M, Maisin J M, Arany Y, Atlan P, Prieto-Cabanis M J, Canal M, Frexinos J
Gastroenterology Unit, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
Aliment Pharmacol Ther. 1995 Oct;9(5):563-9. doi: 10.1111/j.1365-2036.1995.tb00422.x.
To evaluate the effects of various doses of lintopride, a new 5HT-4 antagonist with moderate 5HT-3 antagonist properties, on oesophageal body and lower oesophageal sphincter (LOS) motility in humans.
Eight healthy male volunteers, mean age 22 (19-28) years, without any history of digestive disease or chest pain, were randomized to three doses of lintopride (0.1, 0.3 and 0.5 mg/kg i.v.) and a placebo at 1-week intervals in a double-blind, crossover study. Oesophageal motility was recorded continuously for 4 h after each dose, using perfused catheters inserted at the level of the LOS and in the body of the oesophagus, at 5, 10 and 15 cm from the LOS. Peristalsis was studied during 10 wet swallows, at 30-min intervals (T0-T240 min).
The LOS basal pressure (23.3 +/- 2.0 cmH2O; mean +/- s.d.) remained stable after dosing with placebo to T240. After lintopride, LOS basal pressure increased significantly vs. placebo (AUC comparison: 0.1 mg/kg, P = 0.036; 0.3 mg/kg, P = 0.027; 0.5 mg/kg, P = 0.052). In contrast, the duration and extent of LOS relaxation after swallowing was not affected by any of the three doses of lintopride. The amplitude of peristaltic waves in the oesophagus increased significantly at T30 after lintopride 0.3 mg/kg (34.5 cmH2O, P = 0.020) and 0.5 mg/kg (32.5 cmH2O, P = 0.027), at T60 after 0.3 mg/kg (48.8 cmH2O, P = 0.0009) and 0.5 mg/kg (29.1 cmH2O, P = 0.029) and at T90 after 0.3 mg/kg (34.5 cmH2O, P = 0.0018).
Lintopride significantly increased the LOS basal tone without affecting LOS physiological relaxation after swallowing. Peristaltic waves were also enhanced by lintopride.
评估新型5HT - 4拮抗剂林托必利（具有中度5HT - 3拮抗剂特性）不同剂量对人体食管体部和食管下括约肌（LOS）运动功能的影响。
8名健康男性志愿者，平均年龄22（19 - 28）岁，无任何消化系统疾病或胸痛病史，在一项双盲、交叉研究中，以1周的间隔随机接受三种剂量的林托必利（静脉注射0.1、0.3和0.5 mg/kg）及安慰剂。每次给药后，使用插入LOS水平及距LOS 5、10和15 cm处食管体部的灌注导管，连续记录食管运动功能4小时。在10次湿吞咽过程中研究蠕动，间隔30分钟（T0 - T240分钟）。
给予安慰剂至T240时，LOS基础压力（23.3±2.0 cmH₂O；均值±标准差）保持稳定。给予林托必利后，LOS基础压力较安慰剂显著升高（AUC比较：0.1 mg/kg，P = 0.036；0.3 mg/kg，P = 0.027；0.5 mg/kg，P = 0.052）。相比之下，三种剂量的林托必利均未影响吞咽后LOS松弛的持续时间和程度。0.3 mg/kg（34.5 cmH₂O，P = 0.020）和0.5 mg/kg（32.5 cmH₂O，P = 0.027）林托必利给药后T30时，食管蠕动波幅度显著增加；0.3 mg/kg（48.8 cmH₂O，P = 0.0009）和0.5 mg/kg（29.1 cmH₂O，P = 0.029）给药后T60时增加；0.3 mg/kg（34.5 cmH₂O，P = 0.0018）给药后T90时增加。
林托必利显著增加LOS基础张力，而不影响吞咽后LOS的生理性松弛。林托必利还增强了蠕动波。
