维拉佐酮
维拉佐酮 性质
| 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 |
| 溶解度 | DMSO（少许）、甲醇（少许） |
| 酸度系数(pKa) | 15.98±0.30(Predicted) |
| 形态 | 固体 |
| 颜色 | 淡黄色至米色 |
| 稳定性 | 非常吸湿 |
| CAS 数据库 | 163521-12-8 |
维拉佐酮 用途与合成方法
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。 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。 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。
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5-HT 1A Receptor
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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.
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.
