Fujii K, Okajima M, Kawahori K
Department of Physiology, School of Medicine, Hiroshima University.
Nihon Heikatsukin Gakkai Zasshi. 1988 Jan;24(1):1-12. doi: 10.1540/jsmr1965.24.1.
The action of cisapride on physiological and disturbed gastrointestinal motor function was investigated in conscious and anesthetized dogs and the mechanism of action involved. Regardless of the presence or absence of vagal innervation, administration of cisapride (0.2 mg approximately 1.0 mg/kg body weight, i.v.) during the quiescent period of interdigestive migrating contractions (IMC), induced non-migrating IMC-like motility in the entire gastrointestinal tract from gastric body to distal colon. Administration of cisapride in the digestive state resulted in the excitatory response of increased amplitude of digestive peristalsis and strong IMC-like motility was not observed. All of these excitatory responses in gastrointestinal motility disappeared by the administration of atropine (0.5 mg approximately 0.1 mg/kg body weight, i.v.). Furthermore, the excitatory response in gastrointestinal motility induced by cisapride in anesthetized dogs disappeared by the administration of TTX (10 micrograms/kg of body weight, i.v.). These results suggest that the excitatory action of cisapride on the gastrointestinal motility is based on its mechanism in which cisapride acts on the cholinergic neurones in the gastrointestinal wall to stimulate ACh release, resulting in the increase in gastrointestinal motility. Cisapride caused powerful IMC-like motility in the ileum of animal with pseudo-obstruction-like motor disturbance which had been seen after preparation of Thiry loop (ileum). This motility migrated from the proximal ileum to the Thiry loop and then to the distal ileum. Trimebutine maleate also demonstrated this effect, but metoclopramide and domperidone were ineffective. Administration of cisapride at the doses (0.2 mg approximately 1.0 mg/kg body weight, i.v.) causing stimulated motor response in the gastrointestinal tract did not induce significant secretion of gastric acid, pancreatic juice and bile.
在清醒和麻醉的犬身上研究了西沙必利对生理和紊乱的胃肠运动功能的作用及其作用机制。无论有无迷走神经支配，在消化间期移行性收缩（IMC）的静止期静脉注射西沙必利（0.2毫克约1.0毫克/千克体重），可在从胃体到结肠远端的整个胃肠道诱导出非移行性IMC样运动。在消化状态下给予西沙必利会导致消化蠕动幅度增加的兴奋反应，未观察到强烈的IMC样运动。静脉注射阿托品（0.5毫克约0.1毫克/千克体重）后，所有这些胃肠运动的兴奋反应均消失。此外，在麻醉犬中，静脉注射TTX（10微克/千克体重）可消除西沙必利诱导的胃肠运动兴奋反应。这些结果表明，西沙必利对胃肠运动的兴奋作用基于其作用机制，即西沙必利作用于胃肠壁的胆碱能神经元以刺激乙酰胆碱释放，从而导致胃肠运动增加。西沙必利在制备Thiry袢（回肠）后出现类似假性肠梗阻样运动障碍的动物回肠中引起强烈的IMC样运动。这种运动从回肠近端迁移到Thiry袢，然后再到回肠远端。马来酸曲美布汀也表现出这种作用，但甲氧氯普胺和多潘立酮无效。静脉注射西沙必利导致胃肠道运动反应受刺激的剂量（0.2毫克约1.0毫克/千克体重）不会诱导胃酸、胰液和胆汁的显著分泌。
