Brain-penetrant, orally active, potent and selective neurokinin-1 (NK1) receptor (NK1R; Tachykinin receptor 1) antagonist with antiemetic efficacy in vivo.

Netupitant is a brain-penetrant, orally active, potent and selective neurokinin-1 (NK1) receptor (NK1R; Tachykinin receptor 1) antagonist (Ca+2 mobilization IC₅₀ = 11.2 nM/hNK1 vs. >1 μM/rNK1 & hNK2/3; hNK1/2/3 K_i = 0.95 nM/1.6 μM/1.6 μM) that effectively blocks agonist GR73632-induced foot tapping in gerbils (ID₅₀ = 0.5 mg/kg po 2h prior to 3 pmol/5 μL GR73632/gerbil icv). In addition to antiemetic efficacy against substance P-associated vomiting reflexes, netupitant is also reported to enhance the analgesic effects of electroacupuncture (EA) among humanized mice with sickle cell disease in response to pain in vivo (10 mg/kg/day, i.p.).