Trifluoperazine
(Synonyms: 三氟拉嗪) 目录号 : GC63240
Trifluoperazine (TFP)是一种多巴胺受体拮抗剂，具有抗精神病作用，广泛用于治疗精神分裂症或相关精神病。
Cas No.:117-89-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
U87MG human glioblastoma cells |
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Preparation Method |
Cells were seeded into 96-well plates at a density of 1.5 × 103 cells per well and allowed to attach for 24 hours. Cells were treated with vehicle or the indicated concentrations of Trifluoperazine diluted in complete media for each 24, 48, and 72 hours. Cell proliferation was determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. |
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Reaction Conditions |
0-20µM for 24, 48, and 72 hours |
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Applications |
U87MG cell viability decreased time dependently (24, 48, and 72-hour Trifluoperazine treatment) as well as dose dependently (1, 2, 5, 10, and 20 µmol/L of Trifluoperazine) |
| Animal experiment [2]: | |
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Animal models |
nude mice |
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Preparation Method |
In total 2 × 106 HCT116 cells were subcutaneously injected in rear flank of nude mice (five per group). The TFP (10 mg/kg, intraperitoneal) was administrated to each group for five times, 3 days apart. |
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Dosage form |
Intraperitoneal injection, 10 mg/kg, 5 times, 3 days apart |
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Applications |
Administration of TFP induced remarkably tumor regression with decreased tumor volume. The proliferation index Ki-67 was analyzed and found that TFP was able to reduce the Ki-67 levels in vivo. |
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References: [1]: Kang S, Hong J, Lee J M, et al. Trifluoperazine, a well-known antipsychotic, inhibits glioblastoma invasion by binding to calmodulin and disinhibiting calcium release channel IP3R[J]. Molecular cancer therapeutics, 2017, 16(1): 217-227. |
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Trifluoperazine (TFP) is an antagonist against dopamine receptors, act as antipsychotic agent and is widely used to treat schizophrenia or related psychoses [1,2]. Trifluoperazine is also a well-known calmodulin antagonist [3].
Trifluoperazine significantly restricted the invasion of glioblastoma cells at a concentration higher than 1 µmol/L, with a half-maximal effective concentration at around 10 µmol/L on invasion of U87MG cells by performing Matrigel transwell invasion assay. The ratio of proliferated glioblastoma cells was significantly decreased in TFP-treated cells [4]. Trifluoperazine inhibits cell vitality, proliferation, and induces cell apoptosis of HCT116 cells with IC50 =14 µM [3]. Trifluoperazine (30 µM, 24h) induced pancreatic adenocarcinoma (PDAC) MiaPaCa-2 cell death and decreased in intracellular availability of ATP [5].
Trifluoperazine (5 mg/kg/day) significantly suppressed the glioblastoma growth of the xenograft mice as evidenced by a marked decrease of glioblastoma tumor size in TFP-treated mice at day 21, there was no lung metastasis in TFP-treated group in the skin xenograft model [4]. Administration of TFP induced remarkably tumor regression with decreased tumor volume in the xenograft model of human HCT116 [3]. Trifluoperazine binds and mimics the effect of the genetic inhibition of NUPR1, a stress protein that promotes tumor growth and acts as a strong anticancer drug in vitro and in vivo in xenografted nude mice [6].
References:
[1]. de Oliveira Marques L, Soares B, de Lima M S. Trifluoperazine for schizophrenia[J]. Cochrane Database of Systematic Reviews, 2004 (1).
[2]. Hong M, Jenner P, Marsden C D. Comparison of the acute actions of amine-depleting drugs and dopamine receptor antagonists on dopamine function in the brain in rats[J]. Neuropharmacology, 1987, 26(2-3): 237-245.
[3]. Qian K, Sun L, Zhou G, et al. Trifluoperazine as an alternative strategy for the inhibition of tumor growth of colorectal cancer[J]. Journal of cellular biochemistry, 2019, 120(9): 15756-15765.
[4]. Kang S, Hong J, Lee J M, et al. Trifluoperazine, a well-known antipsychotic, inhibits glioblastoma invasion by binding to calmodulin and disinhibiting calcium release channel IP3R[J]. Molecular cancer therapeutics, 2017, 16(1): 217-227.
[5]. Huang C, Lan W, Fraunhoffer N, et al. Dissecting the anticancer mechanism of trifluoperazine on pancreatic ductal adenocarcinoma[J]. Cancers, 2019, 11(12): 1869.
[6]. Neira J L, Bintz J, Arruebo M, et al. Identification of a drug targeting an intrinsically disordered protein involved in pancreatic adenocarcinoma[J]. Scientific reports, 2017, 7(1): 1-15.
| Cas No. | 117-89-5 | SDF | |
| 别名 | 三氟拉嗪 | ||
| 分子式 | C21H24F3N3S | 分子量 | 407.5 |
| 溶解度 | DMSO : 50mg/mL | 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 | 2.454 mL | 12.2699 mL | 24.5399 mL |
| 5 mM | 0.4908 mL | 2.454 mL | 4.908 mL |
| 10 mM | 0.2454 mL | 1.227 mL | 2.454 mL |
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| 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，
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1. 首先保证母液是澄清的；
2.
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Trifluoperazine for schizophrenia
Cochrane Database Syst Rev 2004;2004(1):CD003545.PMID:14974020DOI:10.1002/14651858.CD003545.pub2.
Background: Trifluoperazine is an inexpensive accessible 'high potency' antipsychotic drug, widely used to treat schizophrenia or related psychoses. Objectives: To estimate the effects of Trifluoperazine compared with placebo and other drugs. Search strategy: Searches of the Cochrane Schizophrenia Group's register of trials (March 2002), supplemented with hand searching, reference searching, personal communication and contact with industry. Selection criteria: All clinical randomised trials involving people with schizophrenia and comparing Trifluoperazine with any other treatment. Data collection and analysis: Studies were reliably selected and quality rated and data was extracted. For dichotomous data, relative risks (RR) were estimated, with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, the number needed to treat (NNT) was calculated. We estimated heterogeneity (I-square technique) and publication bias. Main results: 1162 people from 13 studies were randomised to Trifluoperazine or placebo. For global improvement, small short-term studies favoured Trifluoperazine (n=95, 3 RCTs, RR 0.62 CI 0.49 to 0.78 NNT 3 CI 2 to 4). Loss to follow up was about 12% in both groups (n=280, 7 RCTs, RR 0.99 CI 0.62 to 1.57) and more people allocated Trifluoperazine used antiparkinson drugs to alleviate movements disorders compared with placebo (n=195, 4 RCTs, RR 5.06 CI 2.49 to 10.27, NNH 4 CI 2 to 9). 2230 people from 49 studies were randomised to Trifluoperazine or another older generation antipsychotic. Trifluoperazine was not clearly different in terms of 'no substantial improvement' (n=1016, 27 RCTs, RR 1.06 CI 0.98 to 1.14) or leaving the study early (n=930, 22 RCTs, RR 1.15 CI 0.83 to 1.58). Almost identical numbers of people reported at least one adverse event (60%) in each group (n=585, 14 RCTs, RR 0.99 CI 0.87 to 1.13), although Trifluoperazine was more likely to cause extrapyramidal adverse effects overall when compared to low potency antipsychotics such as chlorpromazine (n=130, 3 RCTs, RR 1.66 CI 1.03 to 2.67, NNH 6 CI 3 to 121). One small study (n=38) found no clear differences between Trifluoperazine and the atypical drug, sulpiride. Reviewer's conclusions: Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that Trifluoperazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs. It has been claimed that Trifluoperazine is effective at low doses for patients with schizophrenia but this does not appear to be based on good quality trial based evidence.
Trifluoperazine versus low-potency first-generation antipsychotic drugs for schizophrenia
Cochrane Database Syst Rev 2014 Jul 8;(7):CD009396.PMID:25003310DOI:10.1002/14651858.CD009396.pub2.
Background: Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between any other antipsychotic compounds, however, low-potency antipsychotic drugs are often perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side-effects. Objectives: To review the effects in response to treatment of Trifluoperazine and low-potency antipsychotics for people with schizophrenia. Search methods: We searched the Cochrane Schizophrenia Group's Trials Register (November 2010). Selection criteria: We included all randomised trials comparing Trifluoperazine with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Main results: The review currently includes seven randomised trials involving 422 participants that compared Trifluoperazine with low-potency antipsychotic drugs. The size of the included studies was between 20 and 157 participants with a study length between four and 52 weeks. Overall, sequence generation, allocation procedures and blinding were poorly reported. Trifluoperazine was not significantly different from low-potency antipsychotic drugs in terms of response to treatment (Trifluoperazine 26%, low-potency drug 27%, 3 RCTs, n = 120, RR 0.96 CI 0.59 to 1.56, moderate quality evidence). There was also no significant difference in acceptability of treatment with equivocal number of participants leaving the studies early due to any reason (Trifluoperazine 20%, low-potency antipsychotics 16%, 3 RCTs, n = 239, RR 1.25, CI 0.72 to 2.17,low quality evidence). There was no significant difference in numbers with at least one adverse effect (Trifluoperazine 60%, low-potency antipsychotics 38%, 1 RCT, n = 60, RR 1.60, CI 0.94 to 2.74, moderate quality evidence). However, at least one movement disorder was significantly more frequent in the Trifluoperazine group (Trifluoperazine 23%, low-potency antipsychotics 13%, 2 RCTs, n = 123, RR 2.08 CI 0.78 to 5.55, very low quality evidence) as well as incoordination (Trifluoperazine 20%, low-potency antipsychotics 5%, 1 RCT, n = 60, RR 7.00, CI 1.60 to 30.66) and rigor (Trifluoperazine 45%, low-potency antipsychotics 10%, 1 RCT, n = 60, RR 4.50, CI 1.58 to 12.84). No data were available for other outcomes of interest death, sedation and quality of life. Authors' conclusions: The results did not show a difference in efficacy between Trifluoperazine and low-potency antipsychotics. Trifluoperazine produced more movement disorders. The number of randomised studies as well as their quality is low, the quality of evidence for outcomes of interest ranged from moderate to very low quality, so more, newer studies would be needed for conclusions about the relative effects of Trifluoperazine and low-potency antipsychotics.
Trifluoperazine versus placebo for schizophrenia
Cochrane Database Syst Rev 2014 Jan 11;2014(1):CD010226.PMID:24414883DOI:10.1002/14651858.CD010226.pub2.
Background: Trifluoperazine is a long-established high potency typical antipsychotic drug used in the treatment of schizophrenia and schizophrenia-like illnesses. Objectives: To determine absolute effects of Trifluoperazine for schizophrenia and schizophrenia-like illnesses compared with placebo.To critically appraise and summarise current evidence on the resource use, cost and economic evaluation of Trifluoperazine compared with placebo for schizophrenia. Search methods: Searches of the Cochrane Schizophrenia Group's register of trials (July 2012), supplemented with handsearching, reference searching, personal communication and contact with industry. Two review authors undertook a search for economic studies using the Cochrane Schizophrenia Group's Health Economic Database (CSzGHED) on the 9th April 2013. Selection criteria: All available clinical randomised trials involving people with schizophrenia and schizophrenia-like illnesses that compare Trifluoperazine with placebo. Data collection and analysis: Studies for the effects of interventions were reliably selected by a review team and data were doubly independently extracted to reduce bias. We only used dichotomous data, using intention-to-treat analysis when possible. Data were estimated using risk ratio (RR) with 95% confidence intervals (CI). A 'Summary of findings' table was produced, where possible, for each primary outcome using GRADE. Economic studies were searched and reliably selected by review authors (VF and SS) to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary. Main results: This review included 10 studies with a total number of 686 participants featuring in 20 different outcomes of interest. Overall, there was significant clinical improvement in clinical global state at medium term amongst people receiving Trifluoperazine (3 RCTs, n = 417, RR 4.61, CI 1.54 to 13.84, low quality evidence) and significantly fewer people receiving Trifluoperazine left the studies early due to relapse or worsening at medium term (2 RCTs, n = 381, RR 0.34, CI 0.23 to 0.49, low quality evidence). However, results were equivocal for leaving the study early at medium term for any reason (2 RCTs, n = 391, RR 0.80, CI 0.17 to 3.81, very low quality evidence) and due to severe adverse effects (2 RCTs, n = 391, RR 1.54, CI 0.56 to 4.24, very low quality evidence). Equivocal data were also found for intensified symptoms at medium term (2 RCTs, n = 80, RR 1.05, CI 0.54 to 2.05, very low quality evidence) and rates of agitation or distress again at medium term (1 RCT, n = 52, RR 2.00, CI 0.19 to 20.72, very low quality evidence). Comparison between low and high-dose Trifluoperazine with placebo from a single study provided equivocal evidence of effects. For economic outcomes, we valued outcomes in GBP terms and presented them in additional tables; there was an estimated saving of £3488.3 in favour of Trifluoperazine. However, numerous assumptions were made and these savings need to be interpreted in light of those assumptions. Authors' conclusions: Our results agree with existing evidence that compared to placebo, Trifluoperazine is an effective antipsychotic for people with schizophrenia. Furthermore, our review provides supportive evidence that Trifluoperazine increases the risk of extrapyramidal adverse effects. Although the effect sizes against placebo are similar to those observed with other agents, they are based on data from many small, pre-CONSORT trials with generally either a low or very low GRADE evidence that has limited implication for clinical practice. Large, independent trials are needed that adhere to the CONSORT statement to compare Trifluoperazine with placebo used in the treatment of schizophrenia and schizophrenia-like illnesses.
Inhibition of dengue virus infection by Trifluoperazine
Arch Virol 2022 Nov;167(11):2203-2212.PMID:35920983DOI:10.1007/s00705-022-05555-y.
Dengue virus (DENV), a member of the genus Flavivirus, family Flaviviridae, is the most widespread viral pathogen transmitted to humans by mosquitoes. Despite the increased incidence of DENV infection, there are no antiviral drugs available for treatment or prevention. Phenothiazines are heterocyclic compounds with various pharmacological properties that are very adaptable for drug repurposing. In the present report, we analyzed the antiviral activity against DENV and the related Zika virus (ZIKV) of Trifluoperazine (TFP), a phenothiazine derivative in clinical use as an antipsychotic and antiemetic agent. TFP exhibited dose-dependent inhibitory activity against the four DENV serotypes and ZIKV in monkey Vero cells at non-cytotoxic concentrations with 50% effective concentration values in the range 1.6-6.4 µM. A similar level of antiviral efficacy was exhibited by TFP against flavivirus infection in the human cell lines A549 and HepG2. Mechanistic studies, performed using time-dependent infectivity assays, real-time RT-PCR, Western blot, and immunofluorescence techniques, indicated that uncoating of the virus during penetration into the cell was the main target for TFP in infected cells, but the compound also exerted a minor effect on a late stage of the virus multiplication cycle. This study demonstrates that TFP, a pharmacologically active phenothiazine, is a selective inhibitor of DENV multiplication in cell culture. Our findings open perspectives for the repositioning of phenothiazines like TFP with a wide spectrum of antiviral efficacy as potential agents for the control of pathogenic flaviviruses.
Trifluoperazine Synergistically Potentiates Bortezomib-Induced Anti-Cancer Effect in Multiple Myeloma via Inhibiting P38 MAPK/NUPR1
Tohoku J Exp Med 2022 Jul 22;257(4):315-326.PMID:35644544DOI:10.1620/tjem.2022.J044.
Multiple myeloma (MM) is a common hematological malignancy. Bortezomib (BTZ) is a traditional medicine for MM treatment, but there are limitations for current treatment methods. Trifluoperazine (TFP) is a clinical drug for acute and chronic psychosis therapy. Lately, researchers have found that TFP can suppress tumor growth in many cancers. We attempted to study the effects of BTZ and TFP on MM in vivo and in vitro. We concentrated on the individual and combined impact of BTZ and TFP on the proliferation and apoptosis of MM cells via Cell Counting kit-8 assay, EdU assay, western blot, and flow cytometry. We found that combination therapy has a strong synergistic impact on MM cells. Combination therapy could induce cell arrest during G2/M phase and induce apoptosis in MM cells. Meanwhile, BTZ combined with TFP could play a better role in the anti-MM effect in vivo through MM.1s xenograft tumor models. Furthermore, we explored the mechanism of TFP-induced apoptosis in MM, and we noticed that TFP might induce MM apoptosis by inhibiting p-P38 MAPK/NUPR1. In summary, our findings suggest that TFP could synergistically enhance the BTZ-induced anti-cancer effect in multiple myeloma, which might be a promising therapeutic strategy for MM treatment.