Nausea is one of a cluster of symptoms described subjectively by patients with delayed gastric emptying. The mechanisms and treatments are unclear (
anti-emetic drugs are not fully effective against
nausea). Can
nausea be relieved by stimulating gastric emptying?
Physostigmine (together with
atropine) has been shown experimentally to stimulate gastric motility, relieve
nausea and restore normal gastric motility. Is this mimicked by gastric prokinetic drugs? The answer is complicated by mixed pharmacology.
Metoclopramide increases gastric motility by activating myenteric 5-HT4 receptors but also directly inhibits
vomiting via D2 and
5-HT3 receptor antagonism; relationships between increased gastric motility and relief from
nausea are therefore unclear. Similarly, the D2 receptor antagonist
domperidone has direct
anti-emetic activity. Nevertheless, more selective 5-HT4 and
motilin receptor agonists (
erythromycin, directly stimulating gastric motility) inhibit
vomiting in animals; low doses of
erythromycin can also relieve symptoms in patients with
gastroparesis.
Ghrelin stimulates gastric motility and appetite mostly via vagus-dependent pathways, and inhibits
vomiting in animals. To date,
ghrelin receptor activation has failed to consistently improve gastric emptying or symptoms in patients with
gastroparesis. We conclude that
nausea can be relieved by gastric prokinetic drugs, but more clinical studies are needed using drugs with selective activity. Other mechanisms (e.g.
ghrelin, vagal and central pathways, influencing a mechanistic continuum between appetite and
nausea) also require exploration. These and other issues will be further explored in a forthcoming special issue of the European Journal of Pharmacology, which focusses on mechanisms of
nausea and
vomiting.