Effects of cisapride on the motility of the digestive tract in dogs and guinea pigs

Abstract

Effects of cisapride on the motility of the digestive tract in vivo in dogs and the guinea-pig intestine in vitro were studied. Cisapride (0.05-2.0 mg/kg, i.v.) produced an increase in amplitude of spontaneous contractions and basal tone in the stomach, duodenum, jejunum and proximal and distal colon in dogs. In some animals, however, it induced an inhibition with decrease in amplitude and tone. It also induced an increase in amplitude of contractions in the gallbladder and the sphincter of Oddi in dogs. The tone of the gallbladder was elevated by the same dose of cisapride, but the tone of the sphincter of Oddi was decreased. The drug produced a reverse response in some animals. These excitatory responses to cisapride were abolished by atropine (0.2 mg/kg, i.v.). Motility of the guinea-pig isolated ileum and colon was enhanced with an increase in their amplitude of contractions and basal tone at low concentrations of cisapride (10(-9)-10(-6)M) but it was inhibited at higher concentrations (10(-5)-10(-4)M). Atropine abolished the excitatory response of the ileum to cisapride in all cases. It abolished the excitation of the colon in some preparations but reduced only in some degree in the other. The inhibitory effect of cisapride on isolated preparations was unaffected by tetrodotoxin. From these results, it is concluded that cisapride enhances motility of the gastrointestinal tract and biliary tract by acting on myenteric cholinergic neurons and inhibits it by acting on the smooth muscle itself.