The introduction of
serotonin 5-HT3 receptor antagonists into clinical practice allowed for a dramatic improvement in the management of
nausea and
vomiting. Despite this, postoperative and
chemotherapy-induced
emesis remains a significant, unresolved issue in many patients even when a combination of
antiemetic drugs is used. Numerous
neurotransmitters have been implicated in triggering
emesis; however, the
tachykinin substance P, by virtue of its localisation within both the gastrointestinal vagal afferent nerve fibres and brainstem
emetic circuitry, and its ability to induce
vomiting when administered intravenously, is thought to play a key role in
emetic responses. Because
substance P is the most likely endogenous
ligand for the neurokinin-1 (NK1) receptor, the development of nonpeptide NK1 receptor antagonists led scientists to evaluate these compounds as
antiemetics. The five NK1 receptor inhibitors that have been studied initially in humans are:
vofopitant (GR-205171),
CP-122721,
ezlopitant (CJ-11974),
MK-869 (L-754030) and its
prodrug L-758298. Except for monotherapy in acute
cisplatin-induced
emesis, this new class of drugs has proven to be highly effective in the control of both
chemotherapy-induced
nausea and
vomiting, and
postoperative nausea and vomiting. No major adverse event was reported in the preliminary trials. Further investigation is mandatory in order to assess the optimal treatment regimen and to make sure the wide spectrum activity of the NK1 receptor inhibitors does not cause significant adverse effects in the context of the treatment of
nausea and
vomiting.