Aprepitant是选择性和高亲和力的神经激肽1受体拮抗剂，Kd值为86 pM。

Aprepitant is a Substance P/Neurokinin-1 Receptor Antagonist. The mechanism of action of aprepitant is as a Neurokinin 1 Antagonist, and Cytochrome P450 3A4 Inhibitor, and Cytochrome P450 2C9 Inducer, and Cytochrome P450 3A4 Inducer.

在疼痛冲动从外周受体到CNS 的传感中,Aprepitant起关键作用,并参与对压力的各种行为及神经化学和心血管的反应.Aprepitant可穿透血脑屏障并与大脑中NK-1受体结合.Aprepitant可抑制化疗引起的细胞毒性,如顺铂（阻断P物质）诱发的急性和延迟性呕吐.Aprepitant（3 mg/kg,i.v.或p.o.）可抑制顺铂（10 mg/kg,i.v.）引起的呕吐.Aprepitant（0.1 mg/kg,i.v.）与地塞米松（20 mg/kg,i.v.）或5–HT3 受体拮抗剂恩丹西酮（0.1 mg/kg,i.v.）联用可加强止吐效果.在雪貂急性迟缓性呕吐模型中,顺铂（5 mg/kg,i.p.）给药后恶心并呕吐的回应记录为72 h.Aprepitant（4-16 mg/kg,p.o.）预处理可剂量依赖性地抑制顺铂引起的呕吐.Aprepitant（2-4 mg/kg/day,p.o.）完全抑制了所有给药雪貂的恶心和呕吐症状.通过注射顺铂24 h后可形成呕吐急性期,开始每天给药,顺铂注射后 24 和48 h,Aprepitant（4 mg/kg,p.o.） 抑制了75%雪貂的恶心和呕吐症状.

Aprepitant对人NK1受体的选择性是人NK3受体的3000倍,比人NK2受体多出50,000倍。在使用人类和动物组织(IC50>3 μM)进行的单胺摄取位点(NE, 5–HT, DA)计数筛选中,以及在人类单胺氧化酶A和B试验以及人类血清素5–HT1A, 5–HT2A, 5–HT2c, 5–HT3, 5–HT5, 5–HT6,和5–HT7 受体(IC50>3 μM)中,Aprepitant均是无活性的。Aprepitant与CNS和外周的NK-1受体结合而拮抗P物质。CHO或 COS 细胞中hNK1受体上50%的P物质会被Aprepitant（0.1 nM）取代。在放射性配体结合试验中,在放射性配体结合筛选的PANLABS 板中,采用原生动物组织,Aprepitant抑制大鼠颌下腺中[3H]P物质与天然NK1受体结合；经检查PANLABS筛选,Aprepitant与其他任何原生动物G蛋白耦合的受体或离子通道均无明显的相互作用。

Aprepitant is dissolved in DMSO. The inhibitory effect of aprepitant on metabolic activity of Nalm-6 cells is assessed by uptake of thiazolyl blue tetrazolium bromide (MTT) by viable cells. Cells are plated onto 96-well plates at a density of 5000 cells/well. After treatment with aprepitant at 5, 10, 15, 20 and 30 μM for 24, 36 and 48 h, the cells are further incubated with 100 μL of MTT (0.5 mg/mL) at 37°C for 3 h. Untreated cells are defined as the control group. Following solubilization of precipitated formazan with 100 μL of DMSO, the optical densitometry is measured with an ELISA reader at a wavelength of 578 nm.

170729-80-3

C23H21F7N4O3

534.435

MK-0869;L-754030;阿瑞匹坦;Aprepitant`;MK-869

DMSO:99 mg/mL (185.2 mM)
Ethanol:12 mg/mL (22.5 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years