Chemotherapy-induced nausea and vomiting (CINV) is common in patients receiving moderately or highly emetogenic chemotherapy and is caused by the activation of peripheral and central nervous system pathways, with the neurokinin-1 receptor playing a central role in delayed CINV. Neurokinin-1 receptor antagonists (NK1RAs) in combination with other antiemetic agents are recommended in international and Chinese guidelines for the prevention of acute and delayed CINV. Therefore, a summary of current data for NK1RAs would be of great clinical utility. This article summarizes the available clinical and real-world data on the use of NK1RAs in CINV prophylaxis, with a focus on evidence from China, where three NK1RAs, aprepitant, fosaprepitant and netupitant, are currently approved. NK1RAs have demonstrated efficacy and favorable safety in the prevention of acute and delayed CINV. Further research is required to determine the optimal use of these drugs and to identify strategies for CINV management in specific patient populations.
Humans ; Vomiting/prevention & control* ; Neurokinin-1 Receptor Antagonists/therapeutic use* ; Nausea/prevention & control* ; Antiemetics/therapeutic use* ; Antineoplastic Agents/adverse effects* ; Aprepitant/therapeutic use* ; Morpholines/therapeutic use*

OBJECTIVETo investigate the influence of non-peptide neuro-kinase 1 (NK1) receptor antagonist L-703, 606 on the early tissue edema formation in rats with deep partial-thickness scald.

METHODSOne hundred and fifty-two SD rats were enrolled in the study and were randomly divided into normal control (NC, n = 8), scald control (SC, n = 48, with 20% TBSA deep partial thickness scald), L-703, 606 treatment (LT, n = 48, with 20% TBSA deep partial-thickness scald 20 minutes after caudal vein injection of 250 nmol/kg L-703, 606) and beta-aescin treatment (AT, n = 48, with 20% TBSA deep-partial-thickness scald 30 minutes after caudal vein injection of 1.8 mg/kg beta-aescin) groups. The rats were sacrificed at 1, 4, 8, 24, 48 and 72 post scald hours (PSHs), with 8 rats at each time point. The peri-wound tissue and jejunum samples were harvested for the detection of vascular permeability and tissue water content with modified Evans blue extravasation method and average water content assay.

RESULTSThe vascular permeability was significantly higher in the peri-wound tissue and jejunum in SC, LT an AT groups than that in NC group (P < 0.01) at 1 PSH, and it decreased gradually at 4 PSH. The vascular permeability in the peri-wound tissue in LT and AT group was significantly lower than that in SC group (P < 0.01), and that in LT group was markedly higher than that in AT group (P < 0.01) at 48 and 72 PSHs. The vascular permeability of jejunum tissue in LT group was lower than that in SC group within 24 PSH (P < 0.01), while that in AT group was lower than that in LT group at the early postscald stage (P < 0.01), but no obvious difference was found between the two groups after 72 PSH (P > 0.05). The change in the tissue water content was as follows: Dehydration was observed in peri-wound tissue in SC, LT and AT groups at 1 PSH. The tissue water content increased gradually thereafter and reached the peak at 8 and 24 PSH. Certain degree of dehydration was observed in jejunum tissue in SC, LT and AT groups at early postscald stage. The water content in jejunum tissue in LT group was evidently higher than that in SC and AT groups (P < 0.05 or 0.01), edema was evident at 8 PSH, and it became more obvious at 48 PSH, then it subsided gradually. Edema was less evident in LT group.

CONCLUSIONNonpeptide NK1-receptor antagonist L-703, 606 was able to mitigate the vascular permeability and reduce tissue water content in peri-wound and jejunal tissues.

Animals ; Burns ; metabolism ; Capillary Permeability ; Disease Models, Animal ; Edema ; drug therapy ; Neurokinin-1 Receptor Antagonists ; Quinuclidines ; therapeutic use ; Rats ; Rats, Sprague-Dawley