Netupitant

Netupitant (CID-6451149) is a highly potent, selective and orally active neurokinin-1 (NK₁) receptor antagonist with a K_i of 0.95 nM for hNK₁ in CHO cells. Netupitant has antiemetic affect^[1][2][3]. In Vitro: Netupitant (CID-6451149) binds with high affinity the human NK₁ receptor (pK_i=9.0) with more than 1000 fold selectivity over the NK₂ and NK₃ (pK_i=5.8 for both sites)^[2].
Netupitant (1, 10, 100 nM) concentration-dependently antagonizes the stimulatory effects of substance P (SP) showing insurmountable antagonism (pK_B=8.87) in CHO NK₁ cells^[2].
In Vivo: Netupitant (CID-6451149; 1-10 mg/kg; ip) dose-dependently inhibits SP-elicited the typical scratching, biting and licking response in mice. In gerbils, foot tapping behavior evoked by the intracerebroventricular injection of a NK₁ agonist is dose-dependently counteracted by Netupitant given intraperitoneally (ID₅₀ 1.5mg/kg) or orally (ID₅₀ 0.5mg/kg)^[2].
Netupitant (0.1-3 mg/kg; i.v.) produces a concentration-dependent inhibition (mean pK_B=9.24) of the responses to SP-methylester (SP-OMe) in the detrusor muscle. Netupitant decreases the frequency of reflex bladder contractions^[3].