The potential for μ-opioid receptor agonists to be anti-emetic in humans: a review of clinical data

In animal models of vomiting, mu-opioid (MOP, OP3) receptors mediate both emesis and anti-emesis. mu-receptors within the blood-brain barrier, mediating anti-emesis, are more rapidly accessible to lipid-soluble mu-opioid receptor agonists such as fentanyl than to morphine, and fentanyl has broad-spectrum anti-emetic effects in a number of species. Whether a similar situation exists in humans is not known. A search was performed for clinical studies comparing the emetic side effects of opioids administered peri-operatively in an attempt to identify differences between morphine and more lipid-soluble mu-receptor-selective agonists such as fentanyl. Overall, the evidence appears to suggest that fentanyl and other phenylpiperidines are associated with less nausea and vomiting than morphine, but not all studies support this, and fentanyl-like drugs are associated with nausea and vomiting per se. Good evidence, however, exists to show that fentanyl and alfentanil do not cause more nausea and vomiting than the ultra fast-acting remifentanil. Because remifentanil is cleared rapidly post-operatively, such trials suggest that the emetic side effects of fentanyl and alfentanil are minimal. The clinical evidence, although limited, is at least consistent with the possibility that central mu-opioid receptors may mediate anti-emesis in humans. It is possible that the role of mu-opioid agonists in anti-emesis may become clearer in the future as a result of the use of peripheral mu-opioid receptor antagonists.