盐酸帕罗西汀
| MDL | MFCD00797405 |
| EC | EINECS 616-601-1 |
| 别名 | ParoxetineHCl |
| 英文名称 | Paroxetine Hydrochloride |
| CAS | 78246-49-8 |
| 分子式 | C19H20FNO3·HCl |
| 分子量 | 365.83 |
| 纯度 | ≥98% |
| 单位 | 支 |
| 生物活性 | Paroxetine hydrochloride 是一种抗抑郁药，为高效的五羟色胺再摄取抑制剂，能抑制 GRK2 活性，IC50 值为 14?μM。[1-5] |
| IC50 | 14?μM (GRK2)[3] |
| In Vitro | 帕罗西汀（1μM和10μM）通过抑制GRK2明显抑制CX3CL1诱导的T细胞迁移。帕罗西汀抑制GRK2诱导的ERK活化[1]。帕罗西汀（10μM）减少LPS刺激的BV2细胞中的促炎细胞因子。帕罗西汀（0-5μM）导致对LPS诱导的BV2细胞中TNF-α和IL-1β产生的剂量依赖性抑制。帕罗西汀还抑制脂多糖（LPS）诱导的一氧化氮（NO）产生和BV2细胞中诱导型一氧化氮合酶（iNOS）的表达。帕罗西汀（5μM）阻断LPS诱导的JNK活化并减弱BV2细胞中的基线ERK1/2活性。帕罗西汀缓解小胶质细胞介导的神经毒性，并抑制原代小胶质细胞中LPS刺激的促炎细胞因子和NO [4]。 |
| In Vivo | 帕罗西汀治疗明显减轻了CIA大鼠的症状。帕罗西汀治疗明确预防关节的组织学损伤并减轻T细胞浸润到滑膜组织中。帕罗西汀显示出对抑制滑膜组织中CX3CL1产生的强烈作用[1]。帕罗西汀（20mg / kg /天）减少大鼠的肌细胞横截面积和远端心肌中的ROS形成。帕罗西汀可降低对室性心动过速的易感性。 MI后的帕罗西汀治疗可能通过减少ROS形成来降低LV重塑和对心律失常的易感性[2]。在CCI帕罗西汀治疗组中，帕罗西汀（10 mg / kg，腹腔注射）在第7天和第10天出现痛觉过敏（P <0.01），但在第14天出现疼痛行为减少。此外，帕罗西汀（10 mg / kg）与CCI载体治疗组相比，显着减弱了触觉超敏反应[5]。 |
| 货期 | 1-2个工作日 |
| SMILES | FC1=CC=C([C@H]2[C@H](COC3=CC=C(OCO4)C4=C3)CNCC2)C=C1.Cl |
| 靶点 | 5-HT Receptor |
| 动物实验 | 动物分为两大类：1）先发性和2）损伤后组。每个主要组分为三个不同的亚组：I）CCI载体治疗组，II）假组，和III）CCI帕罗西汀治疗组。将载体ip注射到CCI和假手术动物。在先发制剂研究中，帕罗西汀（10 mg/kg）在手术前1小时注射，并且每天持续至手术后第14天。在损伤后组中，帕罗西汀（10mg/kg）在损伤后第7天给药，并且每天持续至第14天。所有行为测试记录在手术前第0天（对照日）和第1,3,5天。 ，7,10和14后神经损伤。 |
| 细胞实验 | 通过四唑盐3- [4,5-二甲基噻唑-2-基] -2,5-二苯基四唑溴化物（MTT）测定法测定细胞活力。最初将BV2和原代小胶质细胞以1×10 4个细胞/孔和5×10 4个细胞/孔的密度接种到96孔板中。处理后，将MTT（PBS中5mg/mL）加入各孔中，并在37℃下孵育4小时。将得到的甲crystals晶体溶解在二甲基亚砜（DMSO）中。在570nm处测量光密度，结果表示为与对照相比存活细胞的百分比。 |
| 数据来源文献 | [1]. Wang Q, et al. Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. Sci Rep. 2017 Mar 28;7:45364.
[2]. Lassen TR, et al. Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction. Basic Res Cardiol. 2017 May;112(3):26. [3]. Waldschmidt HV, et al. Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine. J Med Chem. 2017 Apr 13;60(7):3052-3069. [4]. Liu RP, et al. Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling. J Neuroinflammation. 2014 Mar 12;11:47. [5]. Zarei M, et al. Paroxetine attenuates the development and existing pain in a rat model of neurophatic pain. Iran Biomed J. 2014;18(2):94-100 |
| 规格 | 50mg 10mM*1mL in DMSO 100mg 500mg |
Paroxetine hydrochloride为高效的五羟色胺再摄取抑制剂，能抑制 GRK2 活性。
使用本产品的应用案例（仅供参考）
In Vivo
Rat（Five-week-old male Sprague-Dawley rats，1.8 mg/kg/day Paroxetine，灌胃）
All rats were kept under a 12 h light/dark cycle at a constant temperature and humidity with ad libitum access to food and water. Rats were allowed to acclimate to housing conditions for a week prior to further treatments. After acclimation, rats were treated with CUMS once a day and lasted for 7 weeks. From 4th to 7th week of CUMS, rats were administrated to L. casei (8×108 CFU/kg/day), paroxetine (1.8 mg/kg/day, a well-known antidepressant purchased from Beijing Jinpan Science &Technology Co.,Ltd., Beijing, China), or equal volume of normal saline by gavage 1 h before they were treated with CUMS, designated L. casei group, positive control group, and CUMS group, respectively. Each rat treated with CUMS was housed separately. Rats only with gavage administration of normal saline without CUMS treatment were used as normal control, and every 5 rats were housed together.
来源文献：Gu F , Wu Y , Liu Y , Dou M , Jiang Y , Liang H . Lactobacillus casei improves depression-like behavior in chronic unpredictable mild stress-induced rats by the BDNF-TrkB signal pathway and the intestinal microbiota. Food Funct. 2020 Jul 1;11(7):6148-6157. doi: 10.1039/d0fo00373e. Epub 2020 Jun 24. PMID: 32578646.