Effect of cisapride on the cholinergic control mechanisms of gastrointestinal motility in dogs.

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.