Neurokinin-1 receptor antagonists: review of their role for the prevention of chemotherapy-induced nausea and vomiting in adults

Abstract

Introduction: The addition of neurokinin-1 receptor antagonists (NK 1 RAs) to standard prophylaxis of 5-hydroxytryptamine-3 RA (5-HT 3 RA) plus dexamethasone more effectively prevents chemotherapyinduced nausea and vomiting (CINV) associated with highly and moderately emetogenic chemotherapy. Areas covered: This review presents the evidence base for the use of oral and intravenous (IV) NK 1 RAs, focusing on the pharmacologic and clinical properties as a class, and highlighting differences between agents. A PubMed literature search was conducted from 2000 to 2018. Expert opinion: Adherence to international antiemetic guidelines remains a clinical challenge. Strategies to simplify antiemetic regimens and facilitate their administration may improve compliance and treatment outcomes. The use of fixed-combination antiemetics offers clinical utility, in combining an NK 1 RA with a 5-HT 3 RA in a single oral dose. The use of long-lasting NK 1 RAs and administering CINV prophylaxis closer to the time of chemotherapy may also assist with guideline and treatment compliance, diminishing the need for home-based administration, and potentially reducing resource utilization. The availability of IV and oral formulations of NK 1 RAs and NK 1 RA-5-HT 3 RA fixed combinations offers further utility, particularly for those patients unsuited for oral administration. However, safety considerations with respect to injection site toxicity and hypersensitivity reactions of the new NK 1 RA IV formulations deserve close attention.

Structures of neurokinin 1 receptor in complex with G q and G s proteins reveal substance P binding mode and unique activation features

“…In the clinic, NK 1 R is today targeted by the two marketed antagonists, aprepitant and netupitant, for the treatment of chemotherapyinduced nausea and vomiting (CINV) (15)(16)(17). Nonetheless, because of their widespread role, NK 1 R ligands may find additional clinical uses, justifying a mechanistic study of this receptor.…”

Prevention of chemotherapy-induced nausea and vomiting in the real-world setting in Spain

“…Alternatively, a quadruplet regimen involving the addition of olanzapine to NK 1 RA + 5-HT 3 RA + DEX is recommended [ 13 , 15 ]. NK 1 RAs approved for the prevention of CINV include aprepitant (oral) and fosaprepitant (IV) in combination with 5-HT 3 RA–DEX, or the fixed-combination agent NEPA (oral), comprising the NK1RA netupitant and the 5-HT 3 RA palonosetron, combined with dexamethasone alone [ 16 ]. The intravenous NEPA formulation was approved in the European Union in early 2020.…”

Simulation of the oxidative metabolization pattern of netupitant, an NK1 receptor antagonist, by electrochemistry coupled to mass spectrometry

“…The quality of life of patients has been a major area of concern over the last decades, with efforts made to improve the palliative care of individuals with terminal illnesses or to relieve the side effects associated with chemotherapy protocols. Netupitant, a relatively new and selective neurokinin-1 (NK 1 ) receptor antagonist, is used either in monotherapy or in combination with palonosetron (a 5-HT 3 receptor antagonist) for the control of unwanted side effects (e.g., nausea and emesis) associated with the postoperative condition or those caused by acute and delayed chemotherapy [ [1] , [2] , [3] , [4] ]. Given the wide distribution of the NK 1 receptors throughout the central and peripheral nervous systems and the omnipresence of the substance P (SP) peptide in all bodily fluids, a better understanding of the SP/NK 1 receptor system is warranted to add to our understanding of how these molecules contribute to the molecular bases of numerous human pathologies, as suggested by Huang and Korlipara [ 5 ] and Muñoz and Coveñas [ 6 ].…”