Studies in animals and man have shown that metoclopramide, bethanechol and domperidone enhance the peristaltic contractions of the esophageal body, increase the muscle tone of the lower esophageal sphincter, and stimulate gastric motor activity. The drugs have been found to be beneficial in the treatment of gastric motor failure and of reflux esophagitis secondary to lower esophageal sphincter incompetence. Metoclopramide and domperidone, unlike bethanechol, do not increase gastric acid secretion. Whilst bethanechol directly stimulates the muscarine receptors of gastrointestinal smooth muscle, metoclopramide is assumed to act indirectly, i.e. through an increase in acetylcholine release. Domperidone antagonizes noradrenaline- and dopamine-induced relaxations of guinea pig isolated smooth muscle preparations. Since there is no evidence for the occurrence of specific dopamine receptors in the esophagus, stomach or ileum of guinea pigs, domperidone is supposed to affect motility, at least in this species, through blockade of α1-adrenoceptors.