Netupitant-d6 is intended for use as an internal standard for the quantification of netupitant by GC- or LC-MS. Netupitant is an insurmountable antagonist of the neurokinin-1 (NK1) receptor (Ki = 0.95 nM in CHO cells expressing the human recombinant receptor).1 It is selective for human NK1 over human NK2 and NK3 and rat NK1 (Kis = >1,500 nM) and over 50 G protein-coupled receptors, monoamine transporters, and ion channels when used in the nanomolar range.2 Netupitant decreases the maximal response to substance P-induced contractions in isolated guinea pig ileum with long-lasting effects. It also dose-dependently inhibits the substance P-induced scratching, biting, and licking response in mice when used at doses ranging from 1 to 10 mg/kg and decreases NK agonist-induced foot tapping in gerbils (ID50s = 1.5 mg/kg, i.p., or 0.5 mg/kg, oral).
|1. Hoffmann, T., B•s, M., Stadler, H., et al. Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists. Bioorg. Med. Chem. Lett. 16(5), 1362-1365 (2006).|2. Rizzi, A., Campi, B., Camarda, V., et al. In vitro and in vivo pharmacological characterization of the novel NK1 receptor selective antagonist Netupitant. Peptides 37(1), 86-97 (2012).