对于怀孕小鼠，氟奋乃静（1 mg/kg；IG）可在妊娠第 6 天至第 15 天诱导妊娠 [5]。哌啶耐药原因：氟奋乃静（0.125–1 mg/kg；IP，单剂量）

Animal/Disease Models: Mice (injection of 60 mg/kg methylphenidate) [6]
Doses: 0.125, 0.25, 0.5, 1 mg/kg
Route of Administration: IP, single dose.
Experimental Results: Antagonizes stereotyped biting caused by methylphenidate; 0.0625-0.5 mg/kg Dramatically inhibits the climbing behavior of mice, and the dose of 1 mg/kg completely eliminates this effect.

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Animal/Disease Models: Mature female Swiss-Webster mice [5]
Doses: 1 mg/kg
Route of Administration: IG, treatment on the 6th to 15th day of pregnancy
Experimental Results: Fetal weight and length were Dramatically diminished, and the sternum and skull were incomplete. The incidence of ossification increases in the bone.

Absorption, Distribution and Excretion
Fluphenazine hydrochloride is rapidly absorbed from the gastrointestinal tract and parenteral routes. After oral or intramuscular administration, fluphenazine hydrochloride typically takes effect within 1 hour; the duration of action is 6-8 hours. In a small study, peak serum fluphenazine concentrations were reached within 1.5-2 hours and 0.5 hours, respectively, after a single intramuscular or oral injection.
Esterification of fluphenazine slows the rate of drug release from adipose tissue, thereby prolonging the duration of action; administration via sesame oil further delays the release rate. After intramuscular injection of decanoic acid fluphenazine dissolved in sesame oil, the onset of action is 24-72 hours; the duration of action is typically 1-6 weeks, with an average of 2 weeks.
Phenothiazines are highly bound to plasma proteins.
The distribution and metabolic pathways of fluphenazine are not fully elucidated. Fluphenazine has been reported to cross the blood-brain barrier; radioactivity was detected in the cerebrospinal fluid of two subjects after intramuscular injection of radiolabeled fluphenazine decanoate. For more complete data on the absorption, distribution, and excretion of fluphenazine (7 types), please visit the HSDB records page. Metabolites/Metabolites In dogs and rhesus monkeys, the major fecal metabolite 7-hydroxyfluphenazine has been isolated and identified by mass spectrometry and nuclear magnetic resonance measurements, involving synthetic 7- and 8-hydroxyfluphenazine. In the bile of treated dogs and rhesus monkeys, 7-hydroxyfluphenazine exists as a glucuronide. Degradation of the piperazine ring in vivo leads to the formation of γ-(phenothiazinyl-10)-propylamine and its ring-substituted analogues CF3-γ-(phenothiazinyl-10)-propylamine and C1-γ-(phenothiazinyl-10)-propylamine.
Fluphenazine and its major metabolites, including fluphenazine sulfoxide, 7-hydroxyfluphenazine, and fluphenazine conjugates, were detected in human plasma, urine, and feces after intramuscular and oral administration of 25 mg (14)C-fluphenazine dihydrochloride.
Adult and newborn rats were treated with psychotropic drugs; the researchers treated the animals with antipsychotic drugs (fluphenazine, beniralidol, pimozide, thiamethoxam), sedatives (oxazepam), and antidepressants (protriptyline) for one year or longer. During this period, the animals' body weight was monitored, and brain weight, total brain lipid content, phospholipid content, (32)P incorporation into each phospholipid, and fatty acid composition of phosphatidylethanolamine were measured. The results showed that long-term use of antipsychotic drugs and antidepressants (but not oxazepam) led to significant changes in phospholipid biochemistry, and these changes were generally biphasic or multiphasic. These variations should be considered when discussing the mechanisms of action and side effects of long-term antidepressants and antipsychotics. More complete metabolite/metabolite data for fluphenazine (6 metabolites) can be found on the HSDB record page. Known human metabolites of fluphenazine include 10-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl}-2-(trifluoromethyl)-10H-5'-phenothiazin-5-one.

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Biological half-life
……The mean terminal half-life (± standard deviation) of fluphenazine is 16.4 ± 13.3 hours. ...
After a single oral dose of fluphenazine hydrochloride, the plasma half-life was 14.7 hours in one patient; after intramuscular injection of fluphenazine hydrochloride, the plasma half-lives were 14.9 hours and 15.3 hours in two patients, respectively. After intramuscular injection of fluphenazine enanthate, the plasma half-lives of the two patients were 3.6 days and 3.7 days, respectively; after intramuscular injection of fluphenazine decanoate, the plasma half-lives of the two patients were 9.6 days and 6.8 days, respectively.

Toxicity Summary
Fluphenazine blocks postsynaptic dopamine D1 and D2 receptors in the mesolimbic system of the brain; it inhibits the release of hypothalamic and pituitary hormones and is thought to inhibit the reticular activating system, thereby affecting basal metabolism, body temperature, arousal, vasomotor tone, and vomiting. Interactions
For patients receiving insulin therapy, it may be necessary to increase the insulin dose or decrease the chlorpromazine dose to maintain glycemic control… Other phenothiazines that may increase glycemic levels include fluphenazine…
Concomitant use of imipramine and chlorpromazine may result in elevated serum concentrations of one of the drugs…Chlorpromazine inhibits the metabolism of imipramine and nortriptyline. Similar precautions should be taken when using other phenothiazines concurrently… Phenothiazines
A 23-year-old male patient with bipolar disorder reported a drug interaction between ascorbic acid and fluphenazine hydrochloride. During 13 days of ascorbic acid replacement therapy, the patient's steady-state plasma concentration of fluphenazine hydrochloride decreased by 25% from baseline. This decrease in concentration is associated with the exacerbation of manic behavior. The mechanism by which ascorbic acid replacement therapy reduces the plasma concentration of fluphenazine hydrochloride may involve not only hepatic enzyme induction but also interactions during the absorption phase. Fluphenazine hydrochloride, along with other QT prolonging drugs including cisapride, erythromycin, and quinidine, may produce additive QT prolongation when used in combination with phenothiazines, increasing the risk of arrhythmias. /Phenothiazines/ For more complete data on interactions of fluphenazine (31 drugs in total), please visit the HSDB record page.

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Non-human toxicity values
Rat intraperitoneal LD50: 100 mg/kg
Rat subcutaneous LD50: 640 mg/kg
Mouse oral LD50: 220 mg/kg
Mouse intraperitoneal LD50: 89 mg/kg
Mouse intravenous LD50: 51 mg/kg

[1]. The neuroleptic drug, fluphenazine, blocks neuronal voltage-gated sodium channels. Brain Res. 2006;1106(1):72-81.

[2]. Based on Principles and Insights of COVID-19 Epidemiology, Genome Sequencing, and Pathogenesis: Retrospective Analysis of Sinigrin and ProlixinRX (Fluphenazine) Provides Off-Label Drug Candidates. SLAS Discov. 2020 Dec;25(10):1123-1140.

[3]. Siragusa S, Bistas KG, Saadabadi A. Fluphenazine. 2022 May 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.

[4]. Peripheral diabetic neuropathy treated with amitriptyline and fluphenazine. JAMA. 1977 Nov 21;238(21):2291-2.

[5]. Teratogenic effect of diphenylhydantoin and/or fluphenazine in mice. J Appl Toxicol. 1996 May-Jun;16(3):221-5.

[6]. Langwiński R, Niedzielski J. Narcotic analgesics and stereotyped behaviour in mice. Naunyn Schmiedebergs Arch Pharmacol. 1980 Jul;312(3):225-7.

Therapeutic Uses
Antipsychotic, phenothiazines; dopamine antagonist. Fluphenazine hydrochloride is indicated for the treatment of manifestations of psychotic disorders. /US product label includes/ Fluphenazine hydrochloride has not been proven effective in treating behavioral complications in patients with intellectual disability. /US product label includes/ Individual variability in the response to antipsychotic medications may be caused by differences in patient adherence, interactions with other drugs, pharmacokinetic differences, and differences in receptor level concentration-response relationships. In some cases, pharmacokinetic differences can be compensated for by individualized dose adjustments based on plasma drug concentration measurements. Previously, differences in patient responses to specific time courses of drug concentration at receptor sites could only be assessed through clinical judgment. New methods for assessing receptor occupancy in vivo promise to measure parameters that at least partially explain individual variability in receptor level drug responses. Monitoring plasma concentrations of fluphenazine, perphenazine, thiothixol, and sulpiride using specific chemical analytical methods appears to provide some guidance for individualized drug dosing. Definite therapeutic plasma concentration ranges for chlorpromazine and haloperidol have not been established. However, when drug toxicity is suspected, monitoring plasma concentrations of chlorpromazine or haloperidol may be valuable and can be used as a means of controlling patient adherence. For more complete data on the therapeutic uses of fluphenazine (6 types), please visit the HSDB record page. Drug Warnings: /Fluphenazine/ Never administer intravenously. ...Extrapyramidal reactions...Quite common, usually of 3 types...Parkinsonian syndrome...Dystonia and dyskinesia, including torticollis, tics, and other involuntary muscle movements...Akasoriatic arthritis, manifested as restlessness...Hyperreflexia has been reported in newborns... /Phenothiazines/ Tardive dyskinesia developed in 12 patients aged 24 to 62 years after taking fluphenazine for 1–2 months to 10 years. Early symptoms of tardive dyskinesia are reversible, and the duration of symptoms before discontinuation is more important than age.
A patient with schizophrenia was admitted to the hospital two days after receiving an intramuscular injection of 50 mg fluphenazine heptahydrate. The abnormal secretion of antidiuretic hormone was likely related to the fluphenazine heptahydrate treatment. /Fluphenazine heptahydrate/
For more complete data on drug warnings for fluphenazine (47 total), please visit the HSDB records page.

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Pharmacodynamics
Fluphenazine is a trifluoromethylphenothiazine derivative used to treat schizophrenia and other psychotic disorders. Fluphenazine has not been shown to be effective in treating behavioral complications in patients with intellectual disability.

C22H26N3OF3S

437.5215

437.174

69-23-8

Fluphenazine-d8;1323633-98-2;Fluphenazine dihydrochloride;146-56-5;Fluphenazine dimaleate;3093-66-1

3372

Dark brown viscous oil

1.3±0.1 g/cm3

568.3±50.0 °C at 760 mmHg

268-274℃

297.5±30.1 °C

0.0±1.6 mmHg at 25°C

1.579

4.84

55.25

1

8

6

30

544

0

C1=CC=C2C(=C1)N(CCCN3CCN(CC3)CCO)C4=C(C=CC(=C4)C(F)(F)F)S2

PLDUPXSUYLZYBN-UHFFFAOYSA-N

InChI=1S/C22H26F3N3OS/c23-22(24,25)17-6-7-21-19(16-17)28(18-4-1-2-5-20(18)30-21)9-3-8-26-10-12-27(13-11-26)14-15-29/h1-2,4-7,16,29H,3,8-15H2

2-[4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol

FluphenazineTriflumethazineFluorophenazineFluorfenazineFluorphenazineSiqualine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。