Contractile mechanisms of action of gastroprokinetic agents: Cisapride, metoclopramide, and domperidone

We investigated the contractile mechanisms of action of three putative gastroprokinetic agents (cisapride, metoclopramide, and domperidone) on the linear phase of gastroduodenal emptying of solid meals in six healthy conscious dogs. The spatial and temporal parameters of gastric, pyloric, and duodenal contractions during the entire period of gastroduodenal emptying, during the 60-min period of drug infusion (t(i)), and during the postdrug infusion period (t(pi)) were analyzed by a computer method. Cisapride accelerated the total gastroduodenal emptying time (t(full)), metoclopramide had no significant effect, and domperidone delayed the t(full). None of the drugs had a significant effect on gastroduodenal emptying during t(i). Both cisapride and metoclopramide enhanced the rate of gastroduodenal emptying during t(pi). Cisapride enhanced pyloric and duodenal motor activity but had no significant effect on antropyloroduodenal coordination during t(full) and t(i). During t(pi), cisapride significantly enhanced both the pyloric and duodenal motor activity and antropyloroduodenal coordination. Metoclopramide exhibited only a few significant effects on the frequency, amplitude, duration, and area under contractions in the antrum, pylorus, and duodenum, but it enhanced antropyloroduodenal coordination during t(full) and t(pi). Domperidone decreased the frequency of corporeal, pyloric, and duodenal contractions and deteriorated antropyloroduodenal coordination by decreasing the frequency of contractions propagating from the antrum or the pylorus to the duodenum. Cisapride and metoclopramide, but not domperidone, increased the mean distance of propagation of duodenal contractions during t(full), t(i), and t(pi). We conclude that cisapride is more effective in accelerating gastroduodenal emptying because it stimulates the largest number of parameters of gastropyloroduodenal contractions that enhance gastric emptying. Most enhancement of gastric emptying rate with both cisapride and metoclopramide occurs during t(pi).