Aprepitant is a novel and highly selective Neurokinin-1 (NK-1) receptor antagonist[1]. Aprepitant has a Kd value of 86pM for the human NK-1 receptor, and IC50 values of 0.1nM, 4nM, and 0.7nM for human, rat, and ferret NK-1 receptors, respectively[2].
In vitro, treatment with Aprepitant (5-30μM) for 24-48h exerted cytotoxic and anti-proliferative effects on Nalm-6 cells in a dose- and time-dependent manner[3]. IC50 for Aprepitant against HEK 293 cells was >90μM[2]. Aprepitant, at 10-60mM concentrations for 72h, elicits cell growth inhibition in a concentration-dependent manner in all melanoma cell lines[4].
In vivo, Intraperitoneal administration of aprepitant (10mg/kg/d) for 3 days attenuated the expression of Conditioned place preference (CPP) induced by psychostimulants, AMPH and cocaine while enhancing morphine induced CPP[5].
References:
[1] Tattersall FD1, Rycroft W, Cumberbatch M, Mason G, Tye S, Williamson DJ, Hale JJ, Mills SG, Finke PE, MacCoss M, Sadowski S, Ber E, Cascieri M, Hill RG, MacIntyre DE, Hargreaves RJ. The novel NK1 receptor antagonist MK-0869 (L-754,030) and its water soluble phosphoryl prodrug, L-758,298, inhibit acute and delayed cisplatin-induced emesis in ferrets. Neuropharmacology. 2000 Feb 14;39(4):652-63.
[2] Muñoz M, Rosso M. The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug. Invest New Drugs. 2010;28(2):187-193.
[3]Bayati S, Bashash D, Ahmadian S, et al. Inhibition of tachykinin NK1 receptor using aprepitant induces apoptotic cell death and G1 arrest through Akt/p53 axis in pre-B acute lymphoblastic leukemia cells. Eur J Pharmacol. 2016;791:274-283.
[4] Muñoz M, Rosso M, Robles-Frias MJ, et al. The NK-1 receptor is expressed in human melanoma and is involved in the antitumor action of the NK-1 receptor antagonist aprepitant on melanoma cell lines. Lab Invest. 2010;90(8):1259-1269.
[5] Mannangatti P, Sundaramurthy S, Ramamoorthy S, Jayanthi LD. Differential effects of aprepitant, a clinically used neurokinin-1 receptor antagonist on the expression of conditioned psychostimulant versus opioid reward. Psychopharmacology (Berl). 2017;234(4):695-705.
Aprepitant是一种新型的、高选择性的神经激肽-1（NK-1）受体拮抗剂。Aprepitant对人NK-1受体的解离常数为86pM，对人、大鼠和雪貂NK-1受体的IC50值分别为0.1nM、0.4nM和0.7nM。
体外实验中，Aprepitant（5-30μM）处理24-48小时后，会以剂量依赖和时间依赖的方式对Nalm-6细胞产生细胞毒性和抗增殖作用[3]。Aprepitant对HEK 293细胞的IC50值大于90μM[2]。Aprepitant在10-60mM的浓度下处理72小时，对所有黑色素瘤细胞系均表现出浓度依赖性的细胞生长抑制作用[4]。
体内实验中，腹腔注射Aprepitant（10mg/kg/d），连续给药3天，可以减弱精神兴奋剂（如苯丙胺和可卡因）诱导的条件反射（CPP），同时增强吗啡诱导的条件反射[5]。