Vomiting is controlled by the emetic centre which is situated in the floor of the fourth ventricle. The emetic centre represents the final common pathway for stimuli from several sites included the chemoreceptor trigger zone - CTZ - located on the surface of the fourth ventricle, the meninges, cerebral cortex, vestibular apparatus and the gastrointestinal tract via vagus and sympathetic afferents. In the emetic centre and the CTZ there are high concentrations of dopamine receptors with associated cholinergic and H1 receptors.
Metoclopramide, phenothiazines, butyrophenones, and domperidone act mainly by antagonism at the dopamine receptors to reduce vomiting stimuli. Domperidone crosses the blood-brain barrier poorly and has mainly a peripheral action. Metoclopramide also has a peripheral action and increases gastro-oesophageal tone and increases stomach emptying due to a cholinergic effect. Serotonin antagonists such as Ondansetron probably have peripheral effects in the gut and a central action.
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