Pimozide
(Synonyms: 匹莫齐特; R6238) 目录号 : GC10643
Pimozide是一种化学结构新颖、高效且口服长效的神经阻滞剂类多巴胺受体抑制剂，对多巴胺D2、D3和D4 受体的Ki值分别为2.4nM、0.2nM和1.8nM。
Cas No.:2062-78-4
Sample solution is provided at 25 µL, 10mM.
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Pimozide is a chemically novel, highly potent and orally long-acting neuroleptic dopamine receptors inhibitor, with Kis of 2.4nM, 0.2nM and 1.8nM for dopamine D2, D3 and D4 receptors, respectively[1][2]. Dopamine receptors, G protein-coupled receptors comprising the five subtypes D1, D2, D3, D4, and D5, mediate the physiological functions of the catecholaminergic neurotransmitter dopamine, ranging from voluntary movement to hormonal regulation and hypertension[3]. Pimozide is commonly used in research on psychiatric disorders such as schizophrenia, Tourette syndrome, and mania[4].
In vitro, treatment of human MCF-7 and MDA-MB-231 breast cancer cells with Pimozide (4μM; 24h) reduces p62 expression, enhances LC3-I-to-LC3-II conversion, induces cell apoptosis by inhibiting RAF1/ERK phosphorylation, down-regulating Bcl-2/Bcl-xl, up-regulating Bax and activating caspase-9, and promotes autophagy via cAMP up-regulation[5]. Treatment of rabbit coronary arterial smooth muscle cells with Pimozide (3μM; 60s) inhibits Kv currents, shifts the inactivation curve to more negative potentials, prolongs recovery from inactivation, and induces ~17mV membrane depolarization via selective targeting of Kv1.5 channels[6].
In vivo, Pimozide (10mg/kg; i.p.; 24 days) combined with bromocriptine significantly suppressed human bromocriptine-resistant prolactinoma xenograft growth in nude mice, reduced tumor volume by~50 %, and markedly down-regulated Ki67 and CD133 expression[7].
References:
[1] Janssen PA, Niemegeers CJ, Schellekens KH, et al. Pimozide, a chemically novel, highly potent and orally long-acting neuroleptic drug. I. The comparative pharmacology of pimozide, haloperidol, and chlorpromazine. Arzneimittelforschung.1968;18(3):261-279.
[2] Burstein ES, Ma J, Wong S, et al. Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J Pharmacol Exp Ther. 2005;315(3):1278-1287.
[3] Missale C, Nash SR, Robinson SW, Jaber M, Caron MG. Dopamine receptors: from structure to function. Physiol Rev. 1998;78(1):189-225.
[4] Sultana A, McMonagle T. Pimozide for schizophrenia or related psychoses. Cochrane Database Syst Rev. 2000;(2):CD001949.
[5] Jiang G, Zhou X, Hu Y, et al. The antipsychotic drug pimozide promotes apoptosis through the RAF/ERK pathway and enhances autophagy in breast cancer cells. Cancer Biol Ther. 2024;25(1):2302413.
[6] Seo MS, An JR, Heo R, et al. The inhibitory effects of pimozide, an antipsychotic drug, on voltage-gated K+ channels in rabbit coronary arterial smooth muscle cells. Drug Chem Toxicol. 2023;46(2):271-280.
[7] Xiao Z, Liang J, Deng Q, et al. Pimozide augments bromocriptine lethality in prolactinoma cells and in a xenograft model via the STAT5/cyclin D1 and STAT5/Bcl xL signaling pathways. Int J Mol Med. 2021;47(1):113-124.
Pimozide是一种化学结构新颖、高效且口服长效的神经阻滞剂类多巴胺受体抑制剂，对多巴胺D2、D3和D4 受体的Ki值分别为2.4nM、0.2nM和1.8nM[1][2]。多巴胺受体属于G蛋白偶联受体，包含D1、D2、D3、D4和D5五种亚型；它们介导儿茶酚胺类神经递质多巴胺的多种生理功能，包括随意运动、激素调节及高血压等[3]。Pimozide常被用于精神分裂症、Tourette综合征及躁狂等精神疾病的研究[4]。
体外实验中，Pimozide（4μM；24h）处理人MCF-7和MDA-MB-231乳腺癌细胞，可降低p62表达、促进LC3-I向LC3-II的转化，并通过抑制RAF1/ERK磷酸化、下调Bcl-2/Bcl-xl、上调Bax及激活caspase-9 诱导细胞凋亡，同时经cAMP上调促进自噬[5]；Pimozide（3μM；60s）作用于兔冠状动脉平滑肌细胞，可抑制Kv电流、使失活曲线左移、延长失活恢复时间，并通过选择性靶向Kv1.5通道诱导约17mV 的膜电位去极化[6]。
体内实验中，Pimozide（10mg/kg；腹腔注射; 24天）联合溴隐亭显著抑制裸鼠体内人溴隐亭耐药型泌乳素瘤异种移植物的生长，使肿瘤体积减少约50%，并显著下调Ki67和CD133表达[7]。
| Cell experiment [1]: | |
Cell lines | human breast cell lines MCF-7 and MDA-MB-231 |
Preparation Method | The human breast cell lines MCF-7 and MDA-MB-231 were cultured in high glucose Dulbecco’s Modified Eagle’s Medium supplemented with penicillin (100unit/ml), streptomycin (100μg/ml), and 10% fetal bovine serum in an atmosphere of 5% CO2 at 37°C. Cells were exposed to 4μM Pimozide for 24h. The cytotoxic potential of Pimozide was determined by MTT assay. Annexin V-FITC Apoptosis Detection Kit was used to evaluate the percentage of apoptotic cells. |
Reaction Conditions | 4μM; 24h |
Applications | Pimozide inhibits breast cancer cell proliferation and induces cell apoptosis in breast cancer cells. |
| Animal experiment [2]: | |
Animal models | BALB/c nude mice |
Preparation Method | For the tumor grafting experiments, primary cells obtained from human prolactinoma tissues were cultured in complete dMEM/F12 and harvested during the logarithmic phase of growth. After adjusting the cell number based on viability, 1x106 viable cells were subcutaneously injected into the flank of nude mice. A total number of 16 (8 male, 8 female) nude mice were used in our study. Upon arrival, at 6 weeks of age, animals were weighed (18-20 grams), ear tagged, and split into 4 different groups (n=4) following a stratified randomization scheme in order for all groups to have a similar body weight distribution at the beginning. All mice were housed in same-sex groups of 5, in type II polycarbonate cages in individually ventilated caging systems. The animal room had a controlled 12h light/dark cycle (lights on at 6:00 AM), temperature (22±2˚C), and relative humidity (45-65%). Food intake was measured by weighing uneaten pellets. Pimozide (10mg/kg), bromocriptine (20mg/kg) or combined treatment was administered via an intraperitoneal injection into mice in the treatment group for 24 days. Injections were performed from the 6th day after the initial intraperitoneal injection until the 30th day. Tumor volumes were measured every other day. Tumor grafts were removed and processed for further analysis. |
Dosage form | 10mg/kg; i.p.; 24 days |
Applications | Pimozide combined with bromocriptine significantly suppressed human bromocriptine-resistant prolactinoma xenograft growth in nude mice, reduced tumor volume by ~50%, and markedly down-regulated Ki67 and CD133 expression. |
References: | |
| Cas No. | 2062-78-4 | SDF | |
| 别名 | 匹莫齐特; R6238 | ||
| 化学名 | 1-[1-[4,4-bis(4-fluorophenyl)butyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one | ||
| Canonical SMILES | FC1=CC=C(C(CCCN2CCC(N3C(NC4=C3C=CC=C4)=O)CC2)C5=CC=C(F)C=C5)C=C1 | ||
| 分子式 | C28H29F2N3O | 分子量 | 461.6 |
| 溶解度 | ≥ 17.95mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1664 mL | 10.8319 mL | 21.6638 mL |
| 5 mM | 433.3 μL | 2.1664 mL | 4.3328 mL |
| 10 mM | 216.6 μL | 1.0832 mL | 2.1664 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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