Comparative Pharmacology of 5-HT3 Antagonists
Despite that the 5-HT3 receptor antagonist share their mechanism of action, they have different chemical structures and exhibit differences in affinity for the receptor, dose response and duration of effect. Also they are metabolized in different ways, that is different components of the cytochrome P450 (CYP) system are predominate in the metabolism of the antagonists.
The 5-HT3 receptor antagonist have similar activity. However patients who are resistant to one antagonist might benefit from another, possibly because the drugs are metabolized differently. A correlation exists between the number of active CYP 2D6 alleles and the number of vomiting episodes by patients who receive treatment with cisplatin and ondansetron or tropisetron. Patients with multiple alleles tend to be unresponsive to the antiemetic drug and vice versa.
| Drug | Chemical nature |
Receptor antagonists | T1/2 (h) | Metabolism | Dose |
|---|---|---|---|---|---|
| Ondansetron | Carbazole derivative | 5-HT3 receptor antagonist and weak 5-HT4 antagonist | 3.9 hours | CYP1A1/2, CYP2D6, CYP 3A3/4/5 | 0.15 mg/kg |
| Granisetron | Indazole | 5-HT3 receptor antagonist | 9-11.6 hours | CYP3A3/4/5 | 10 µg/kg |
| Dolasetron | Indole | 5-HT3 receptor antagonist | 7–9 hours | CYP 3A3/4/5, CYP2D6 | 0.6–3 mg/kg |
| Palonosetron | Isoquinoline | 5-HT3 receptor antagonist; highest affinity for 5-HT3 receptor in this class | 40 hours | CYP1A2, CYP2D6, CYP3A3/4/5 | 0.25 mg x 1 dose |
| Ramosetron | Benzimidazole derivative | 5-HT3 receptor antagonist | 5.8 hours | 300 µg/kg | |
| Tropisetron | Indole | 5-HT3 receptor antagonist | 5.6 hours | CYP 3A3/4/5, CYP2D6 | 200 µg/kg |
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