Neurokinin-1 antagonists compete with
substance P, an endogenous
ligand with a high density of receptors in the area postrema and the nucleus tractus solitarii, believed to be involved in terminal
emetic pathways. Experimental data provide evidence for efficacy against a wide range of peripheral and central
emetic stimuli and clinical trials confirm that neurokinin-1 antagonists have significantly higher efficacy against
vomiting than all other
antiemetics, with relative risk reductions of over 50%. In fact,
aprepitant - the first neurokinin-1 antagonist approved by the US Food and Drug Administration - provides superior protection against
postoperative vomiting compared with
ondansetron, and the same appears to be true for other drugs of this class. However, efficacy against
nausea does not appear to be superior to other
antiemetics, so that composite outcomes that are driven by
nausea (e.g. complete response) disguise the unique anti-
vomiting efficacy.
SUMMARY: