Chlorpromazine (hydrochloride) 氯丙嗪盐酸盐
| MDL | MFCD00012654 |
| EC | EINECS 200-701-3 |
| 别名 | 氯普马嗪; ?盐酸氯丙嗪 |
| CAS | 69-09-0 |
| 分子式 | C17H19ClN2S·HCl |
| 分子量 | 355.33 |
| 纯度 | HPLC≥98% |
| 单位 | 瓶 |
| 生物活性 | Chlorpromazine Hydrochloride是D2，5HT2A，钾通道和钠通道的拮抗剂。 Chlorpromazine与 D2 和 5HT2A 结合的 Ki 分别为363 nM和8.3 nM。[1-5] |
| IC50 | Ki: 363 nM (dopamine D2 receptor), 8.3 nM (5-HT2A receptor)[4] |
| In Vitro | 氯丙嗪（3,10,20,40和60μM）以浓度依赖性方式降低hNav1.7的峰值电流，IC50为25.9μM，Hill系数为2.3。氯丙嗪（25μM）对hNav1.7电流产生强烈的使用依赖性抑制作用。氯丙嗪阻断hNav1.7通道，不依赖于钙调蛋白[1]。氯丙嗪阻断HERG钾通道，IC50值为21.6μM，Hill系数为1.11。氯丙嗪（1,10,100μM）以浓度依赖性方式阻断非洲爪蟾卵母细胞中表达的HERG钾通道。氯丙嗪在激活状态下阻断HERG钾通道[5]。 |
| In Vivo | 氯丙嗪（2 mg/kg，ip）诱导的神经行为异常（NAs）的特征是小鼠的僵住行为显著增加，自发活动反应时间延长[2]。在大鼠治疗的第5天和第10天，氯丙嗪（1或5 mg/kg，i，p。）可防止氯胺酮（KET）增加δ和γ-高谱带的平均光谱功率[3]。 |
| SMILES | CN(C)CCCN1C2=C(C=CC=C2)SC3=CC=C(Cl)C=C13.Cl |
| 靶点 | Dopamine Receptor |
| 动物实验 | 将体重18-25g的成年小鼠（8-10周龄）分成5组，每组6只小鼠。治疗方案如下：第1组，对照（生理盐水：NS，10mL/kg ip）;第2组，氯丙嗪（CPZ，2 mg/kg ip）;第3组，溴隐亭（BMC，2.5 mg/kg sc）;第4组：氨氯地平（AML，1mg/kg sc）;第5组，BMC（2.5mg/kg sc）+ AML（1mg/kg）。用BMC或AML或其组合治疗的动物也在30分钟后（ip）接受氯丙嗪。对动物进行各种测试，包括用于强直性昏厥的金属棒测试和用于运动评估和敏捷性的自发活动轮以及高架十字迷宫，孔板，Y-迷宫，运动活动的开放场测试和探索行为。 18小时后通过颈椎脱位使动物安乐死。解剖脑，在缓冲液（pH 7.6）中漂洗并用Teflon匀浆并用于评估脂质过氧化，还原型谷胱甘肽，超氧化物歧化酶和过氧化氢酶。 |
| 数据来源文献 | [1]. Lee SJ, et al. Mechanism of inhibition by chlorpromazine of the human pain threshold sodium channel, Nav1.7. Neurosci Lett. 2017 Feb 3;639:1-7
[2]. Kale OE, et al. Amlodipine, an L-type calcium channel blocker, protects against chlorpromazine-induced neurobehavioural deficits in mice. Fundam Clin Pharmacol. 2017 Jan 19 [3]. Sampaio LR, et al. Electroencephalographic study of chlorpromazine alone or combined with alpha-lipoic acid in a model of schizophrenia induced by ketamine in rats. J Psychiatr Res. 2017 Mar;86:73-82 [4]. Suzuki H, et al. Comparison of the anti-dopamine D? and anti-serotonin 5-HT(2A) activities of chlorpromazine, bromperidol, haloperidol and second-generation antipsychotics parent compounds and metabolites thereof. J Psychopharmacol. 2013 Apr;27(4):396-400 [5]. Thomas, D., et al. The antipsychotic drug chlorpromazine inhibits HERG potassium channels. Br J Pharmacol, 2003. 139(3): p. 567-74. |
| 规格 | 10mg 50mg |
是D2，5HT2A，钾通道和钠通道的拮抗剂。也是一种细胞内吞抑制剂。
使用本产品的应用案例（仅供参考）
In Vitro
Cell（HepG2）, 20 µg/mL, 1 h, 37°C
For initial study of cellular internalization, NPs-EPI was incubated with tumor spheroids at an EPI concentration of 8 µg/mL for 4 h. The tumor spheroids were grown as our previous reported procedure. Briefly, HepG2 cells were seeded in 96-well plates at a density of 8×103 per well precoated with 50 µL of 1% low melting point agarose. Cells were cultured to obtain multicellular spheroids (400–500 μm in diameter) for subsequent studies. After incubation with NPs-EPI, tumor spheroids were rinsed three times with cold PBS and processed for image analysis by TEM.
To investigate the internalization pathways of NPs-EPI, HepG2 cells were seeded into 6-well plates with 2×105 cells per well and incubated for 24 hours. The cells were then pre-treated with different endocytic inhibitors (chlorpromazine hydrochloride 20 µg/mL, amiloride hydrochloride 200 µg/mL) at 37°C for 1 hour. Subsequently, NPs-EPI (EPI 8 µg/mL) were added and incubated at 37°C for 2 hours. Finally, the cells were washed three times with cold PBS and harvested for flow cytometry to determine the fluorescence intensity of EPI (Ex=488, Em=588). Cells pre-treated with PBS at 37°C served as the positive control group. Internalization assays were also performed in the absence of endocytic inhibitors at 4°C when indicated.
来源文献：Chen E, Han S, Song B, Xu L, Yuan H, Liang M, Sun Y. Mechanism Investigation of Hyaluronidase-Combined Multistage Nanoparticles for Solid Tumor Penetration and Antitumor Effect. Int J Nanomedicine. 2020 Aug 24;15:6311-6324. doi: 10.2147/IJN.S257164. PMID: 32922003; PMCID: PMC7458542.
Cell ，100 μM，30 min
To investigate the endocytosis mechanism involved in the uptake process, cells were pre-treated with endocytic inhibitors including chlorpromazine (100 μM), genistein (200 μM), and amiloride (200 µM) for 30 min. Ten the cells were treated with 1 μg of FITC-labeled DMSNs for 6 h. In a control group, cells were not treated with the inhibitors prior to nanoparticle treatment. Cellular uptakes of nanoparticles were quantitated by fow cytometer as described above.
来源文献：Mo C, Lu L, Liu D, Wei K. Development of erianin-loaded dendritic mesoporous silica nanospheres with pro-apoptotic effects and enhanced topical delivery. J Nanobiotechnology. 2020 Mar 30;18(1):55. doi: 10.1186/s12951-020-00608-3. PMID: 32228604; PMCID: PMC7104482.