Which of the following antiemetics is most likely to cause sedation?

The correct choice is promethazine, which is an antiemetic known for its sedative properties. Promethazine belongs to a class of medications called phenothiazines, which are primarily used to treat nausea and vomiting but also have significant antihistaminic effects. This antihistaminic action can lead to sedation, making it effective for managing motion sickness and situations where calming effects are desired.

Promethazine's sedative effects are more pronounced compared to other antiemetics. For example, granisetron and ondansetron are both serotonin 5-HT3 receptor antagonists that specifically target nausea and vomiting without significant central nervous system (CNS) effects, making them less likely to cause sedation. Although metoclopramide can have some sedating effects, its primary actions involve increasing gastrointestinal motility and antiemetic properties through dopamine receptor antagonism, rather than producing sedation as a primary effect.

Thus, promethazine stands out in this group as the antiemetic with the highest potential for sedation, making it the most suitable answer to this question.