Which antiemetic agent acts as a selective antagonist of neurokinin-1 (NK1) receptors in the chemoreceptor trigger zone?

Explanation

## Neurokinin-1 Receptor Antagonists **Key Point:** Aprepitant is a selective NK1 receptor antagonist, a novel class of antiemetic distinct from 5-HT3 antagonists and corticosteroids. **High-Yield:** NK1 receptors are activated by substance P, a neuropeptide involved in chemotherapy-induced nausea and vomiting (CINV), particularly delayed emesis (>24 hours post-chemotherapy). ### Mechanism of Action Aprepitant crosses the blood–brain barrier and competitively blocks NK1 receptors in the chemoreceptor trigger zone and vomiting centre. This provides superior control of delayed CINV when combined with 5-HT3 antagonists and corticosteroids. ### Clinical Use - Highly emetogenic chemotherapy (cisplatin-based regimens) - Delayed emesis prevention - Part of triple antiemetic regimen: aprepitant + ondansetron + dexamethasone **Clinical Pearl:** Aprepitant has a long half-life (~40 hours) and is a potent CYP3A4 inhibitor, requiring dose adjustments of concurrent medications metabolized by this enzyme (e.g., warfarin, benzodiazepines). ### Comparison with Other Antiemetics | Agent | Receptor Target | Onset | Best For | |-------|-----------------|-------|----------| | Aprepitant | NK1 antagonist | Slow (crosses BBB) | Delayed CINV | | Ondansetron | 5-HT3 antagonist | Rapid | Acute CINV | | Metoclopramide | D2 antagonist + 5-HT4 agonist | Rapid | Gastric dysmotility | | Dexamethasone | Glucocorticoid (mechanism unclear) | Slow | Delayed CINV adjunct |