Netupitant (hydrochloride)

Netupitant hydrochloride (CID 6451149 hydrochloride) is a blood-brain barrier penetrable, orally active NK1 receptor inhibitor with a K_i of 0.95 nM (CHO cells) against the human receptor. Netupitant hydrochloride antagonizes the effects induced by Substance P, inhibits the maximal response of Substance P with a long-lasting action, and suppresses NK1 agonist-induced behaviors in mice and gerbils. Netupitant hydrochloride reduces the frequency of bladder contractions, prolongs contraction intervals, decreases basal pressure at high doses, and acts on the afferent branch of the micturition reflex. Netupitant hydrochloride can be used in research related to overactive bladder, chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, anxiety disorders, and depression^[1][2][3]. In Vitro:Netupitant hydrochloride potently and selectively inhibits NK1 receptor-mediated contractions in isolated guinea pig detrusor muscle strips, with a mean pK_B value of 9.24^[1].
Netupitant (1-100 nM; 24 min) hydrochloride potently inhibits Substance P (SP)-induced calcium mobilization in CHO cells expressing human NK1 receptors, exhibiting insurmountable antagonism with a pK_B value of 8.87^[2].
Netupitant (1 μM; 24 min) hydrochloride acts as a low-potency surmountable antagonist of Substance P-induced calcium mobilization in HEK293 cells expressing the rat NK1 receptor, with a pK_B value of 6.57^[2].
Netupitant (Compound 21) hydrochloride potently binds to human NK1 receptors expressed in CHO cells, with a K_i value of 0.95 nM, and exhibits at least 100-fold selectivity over NK2 and NK3 receptors^[3]. In Vivo:Netupitant (0.1-3 mg/kg; intravenous administration; 5 min infusion duration) hydrochloride dose-dependently reduces the frequency of bladder contractions without altering contraction amplitude in isovolumetric anesthetized guinea pigs^[1].
Netupitant (0.1-3 mg/kg; intravenous injection; infusion duration 5 min) hydrochloride dose-dependently prolongs the contraction interval without altering the micturition amplitude in anesthetized guinea pigs with acetic acid-induced overactive bladder^[1].
Netupitant (1-10 mg/kg, i.p.; single administration) hydrochloride significantly reduces Substance P-induced nociceptive behaviors such as scratching, gnawing and licking in mice^[2].
Netupitant (0.3-3 mg/kg; i.p.; single dose; 0.1-3 mg/kg; p.o.; single dose) hydrochloride inhibits GR73632 (HY-P1192)-induced foot-tapping behavior in gerbils^[2].