Which antiemetic agent can cause extrapyramidal symptoms if used long-term?

Metoclopramide is the antiemetic agent that can cause extrapyramidal symptoms, particularly when used long-term. This medication works primarily as a dopamine antagonist in the central nervous system, particularly in the area postrema, which is involved in inducing vomiting. However, because it blocks dopamine receptors, long-term use may lead to the development of extrapyramidal symptoms, such as tardive dyskinesia, akathisia, and other movement disorders typically associated with the disruption of dopaminergic pathways.

In contrast, the other agents listed, including granisetron, ondansetron, and palonosetron, are serotonin receptor antagonists that primarily target the 5-HT3 receptors. These medications are less likely to affect dopaminergic pathways, which significantly reduces the risk of extrapyramidal symptoms. Therefore, metoclopramide stands out for its potential to cause these side effects, particularly with prolonged use.