Neurokinin (NK) receptors belong to the family of G-protein coupled receptors and can be divided into three subtypes: NK1, NK2 and NK3. The endogenous ligand for NK1 receptor is the 11 amino acid neuropeptide substance P (SP)[3]. Netupitant is a highly potent and selective, orally active neurokinin-1 receptor antagonist with Ki of 0.95 nM[3]. In CHO NK1 cells, netupitant concentration-dependently antagonized the stimulatory effects of substance P (SP) showing insurmountable antagonism (pK(B) 8.87)[4]. In the guinea pig ileum, netupitant concentration-dependently depressed the maximal response to SP (pK(B) 7.85) and, in functional washout experiments, displayed persistent (up to 5h) antagonist effects. In mice the intrathecal injection of SP elicited the typical scratching, biting and licking response that was dose-dependently inhibited by netupitant given intraperitoneally in the 1-10 mg/kg dose range. In gerbils, foot tapping behavior evoked by the intracerebroventricular injection of a NK1 agonist was dose-dependently counteracted by netupitant given intraperitoneally (ID(50) 1.5mg/kg) or orally (ID(50) 0.5mg/kg)[4].
搜索
