Ondansetron is the antiemetic of choice in chemotherapy-induced nausea. It acts by blocking 5-HT3 receptors. The principal anatomical locations where 5-HT3 blockade produces antiemetic effects are:

• A Substantia nigra and basal ganglia, reducing dopamine-mediated nausea pathways
• B Vagal afferents in the gut and the chemoreceptor trigger zone (area postrema) in the medulla ✓
• C Hypothalamic histamine H1 receptors and vestibular nucleus cholinergic neurons
• D Nucleus accumbens and limbic cortex, reducing anticipatory nausea

Explanation

Chemotherapy-induced nausea involves serotonin (5-HT) released from enterochromaffin cells of the gut mucosa activating 5-HT3 receptors on vagal afferent fibres, which relay signals to the vomiting centre. Additionally, 5-HT3 receptors are present in the chemoreceptor trigger zone (area postrema, outside the blood-brain barrier) where blood-borne emetics activate the vomiting reflex. Ondansetron blocks both these sites. Dopamine D2 receptors (not 5-HT3) in the basal ganglia mediate metoclopramide's EPS; histamine H1 and muscarinic receptors mediate motion sickness.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.