中文名称:

维拉佐酮

中文同义词:

维拉唑酮杂质;维拉佐酮(游离碱);盐酸维拉佐酮C10;盐酸维拉佐酮;维拉佐酮;维拉佐酮盐酸盐;甲基-2H-异吲哚-1,3-二酮;5-(4-(4-(5-氰基-1H-吲哚-3-基)丁基)哌嗪-1-基)苯并呋喃-2-甲酰胺

英文名称:

VILAZODONE

英文同义词:

2-BenzofurancarboxaMide,5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-;Vilazodonei;Vilazodone 5-[4-[4-(5-Cyanoindol-3-yl)butyl]piperazin-1-yl]benzofuran-2-carboxamide;5-(4-(4-(5-Cyano-1H-indol-3-yl)butyl)piperazin-1-yl)benzofuran-2-carboxamide;Verazodone hydrochloride;VIIBRYD; 5-(4-[4-(5-CYANO-1H-INDOL-3-YL)BUTYL]PIPERAZIN-1-YL)BENZOFURAN-2-CARBOXAMIDE;CS-108;5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carboxamide

CAS号:

163521-12-8

分子式:

C26H27N5O2

分子量:

441.52

EINECS号:

1308068-626-2

相关类别:

医药中间体;原料药;小分子抑制剂;医药原料;G蛋白偶联受体G蛋白;陕西林奈主打产品;Other APIs;Amines;Aromatics;Heterocycles;Intermediates Fine Chemicals;Pharmaceuticals

Mol文件:

163521-12-8.mol

熔点 

203-205°C

沸点 

745.1±60.0 °C(Predicted)

密度 

1.34±0.1 g/cm3(Predicted)

储存条件 

Keep in dark place,Sealed in dry,Store in freezer, under -20°C

酸度系数(pKa)

15.98±0.30(Predicted)

CAS 数据库

163521-12-8

适应症

本品为5-羟色胺(HT)1A部分激动剂和选择性5-羟色胺再摄取抑制剂(SSRI)双重活性药物，是首个吲哚烷基胺类抗抑郁药物，适用于重性抑郁障碍(MDD)成年患者的治疗。

抑郁症治疗药物

维拉佐酮是一种选择性血清素再吸收并血清素1A受体抑制剂和部分激动剂，临床上主要用于治疗成人抑郁症。 2011年1月21日美国食品药品监督管理局(FDA)批准盐酸维拉佐酮片用于治疗成年中重度抑郁症。

药物相互作用

维拉唑酮主要经CYP3A4途径代谢，因此当与CYP3A4强抑制剂（如酮康唑）同时使用时，能够增加维拉佐酮血浆浓度，给药剂量应相应降低；当与CYP3A4诱导剂同时使用时则可能降低其疗效。根据维拉佐酮的作用机制及不良反应和5-HT潜在毒性，同时服用本品和其他可能影响5-HT活性神经递质系统的药物（如曲普坦、曲马多等）能够增加血清素综合征和神经阻滞剂恶性综合征（NMS）发生的风险，应慎用；本品和非甾体类抗炎药（NSAIDs）、阿司匹林及华法林同时使用时可能增加异常出血的风险。另外，维拉唑酮不能与单胺氧化酶抑制剂（MAOI）同时使用，在使用维拉佐酮之前或之后至少14d内禁用MAOI类药物。

生物活性

Vilazodone (EMD-68843, SB-659746A)是一种新型抗抑郁剂，具有选择性5-HT再摄取抑制作用和部分5-HT1A受体激动活性。Vilazodone与5-HT重吸收位点的结合亲和力比与去甲肾上腺素和多巴胺位点结合亲和力高。

靶点

5-HT 1A Receptor

5-HT 1A Receptor

体外研究

Vilazodone shows an IC 50 of 0.2 nM at the human 5-HT 1 A receptor and 0.5 nM for the SERT. Vilazodone preferentially binds to the high agonist affinity state of human 5-HT 1 A receptors, and it displays high affinity (pK i ≥9.3) for human recombinant and rat, guinea pig, mouse, and marmoset native tissue 5-HT 1A receptors.Vilazodone acts as a high efficacy partial agonist at 5-HT 1 A receptors. In [ 35 S]GTPγS binding studies in Sf9 cells expressing h5-HT 1 A receptors, a single concentration of Vilazodone (100nM) increases basal binding by approximately 70% of that produced by the full 5-HT 1 A receptor agonist, 8‐OH‐PIPAT. In [ 35 S]GTPγS binding studies in rat hippocampal membranes, Vilazodone acts as a potent 5‐HT 1A receptor partial agonist with a pEC 50 of 8.1 and an intrinsic activity of 0.61. Vilazodone acts as a potent 5‐HT reuptake inhibitor in rat and guinea pig cortex. In LLCPK cells expressing human SERT, whereby vilazodone inhibits [ 3 H]5‐HT uptake with a pIC 50 of 8.8.

体内研究

Vilazodone (intraperitoneal injection; 3 mg/kg ; single dose) produces increases in extracellular levels of 5‐HT in both the frontal cortex (FC) and ventral hippocampus (vHipp) of rats in vivo microdialysis studies. Maximum increases are observed at 3 mg/kg and reaches 527% and 558% of preinjection baseline values in the FC and vHipp, respectively. Vilazodone (oral gavage ;55 mg/kg ; single dose) inhibits stress‐induced vocalizations in the rat ultrasonic vocalizations test at 120 and 210 min post dose.