Pharmacokinetics, pharmacodynamics, safety, and tolerability of dopamine-receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting.

Introduction: Dopamine (D)_2,3-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV).

Areas covered: Eight D_2,3-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects.

Expert opinion: Since the introduction of D_2,3-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)₃-RAs and neurokinin (NK)₁-RAs have been developed. The classical D_2,3-RAs are recommended in the prophylaxis of CINV from low emetic risk chemotherapy, but not as a fixed component of an antiemetic regimen for moderately or highly (HEC) emetic risk chemotherapy. D_2,3-RAs are also used in patients with breakthrough nausea and vomiting. It should be emphasized, that most of these drugs are not selective for dopamine receptors.The multi-receptor targeting agent, olanzapine, is recommended in the prophylaxis of HEC-induced CINV as part of a four-drug antiemetic regimen, including a 5-HT₃-RA, dexamethasone and a NK₁-RA. Olanzapine is the most effective agent to prevent chemotherapy-induced nausea.Side effects differ among various D_2,3-RAs. Metopimazine and domperidone possess a low risk of extrapyramidal side effects. Domperidone and metoclopramide are prokinetics, whereas metopimazine delays gastric emptying and haloperidol does not influence gastric motility. Many D_2,3-RAs increase the risk of prolonged QTc interval; other side effects include sedation and orthostatic hypotension.