| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Fluphenazine targets dopamine receptors, primarily D1DR and D2DR (D1 and D2 dopamine receptors) in the central nervous system. As a typical antipsychotic, Fluphenazine blocks D2 receptors in the mesolimbic pathway (reducing positive symptoms of schizophrenia) and in the nigrostriatal pathway (causing extrapyramidal side effects). The deuterated form has identical target specificity and is used as an internal standard.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
In vitro, Fluphenazine dihydrochloride is a potent dopamine receptor antagonist. The deuterated form (d8) has identical biological activity to the unlabeled compound but is not typically studied for independent bioactivity. Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules largely as tracers for quantitation during the drug development process. Deuteration may affect the pharmacokinetic and metabolic profiles. |
| ln Vivo |
In vivo, Fluphenazine dihydrochloride is used as an antipsychotic medication for the treatment of schizophrenia and other psychotic disorders. The deuterated form (d8) is not administered in vivo for therapeutic purposes. It is used as an internal standard for the accurate quantification of Fluphenazine and its metabolites in biological matrices for pharmacokinetic studies and therapeutic drug monitoring. Deuteration has gained attention because of its potential to affect the PK and metabolic profiles of drugs.
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| Enzyme Assay |
Cell-free receptor-binding assays: Prepare membrane fractions from D1DR or D2DR-expressing cells (e.g., HEK293-D1R or CHO-D2R). Incubate membranes (20-50 ug protein) with 0.1-1 nM [3H]-SCH23390 (for D1) or [3H]-spiperone (for D2) and varying concentrations of Fluphenazine-d8 dihydrochloride (1 pM-10 uM) in binding buffer (50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, pH 7.4) for 60 minutes at 25degC. Terminate by filtration through GF/B filters, wash with cold buffer, and measure retained radioactivity by scintillation counting. Determine IC50 and Ki by nonlinear regression. Use unlabeled Fluphenazine as a control. For isotope use as LC-MS internal standard, prepare calibration curves with unlabeled Fluphenazine and a fixed concentration of Fluphenazine-d8. Use MRM transitions: m/z 438.2 → 171.1 (unlabeled) and m/z 446.2 → 179.1 (d8).
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| Cell Assay |
Culture dopamine D2 receptor-expressing cells (e.g., rat pituitary GH3 cells, mouse striatal neurons, or SH-SY5Y neuroblastoma cells) in appropriate medium. Treat cells with Fluphenazine-d8 (0.1-10 uM) for 6-48 hours. For cAMP assays, treat cells with forskolin (10 uM) and varying concentrations of Fluphenazine-d8 (0.1 nM-10 uM) for 15-30 minutes. Lyse cells and measure cAMP by ELISA. For proliferation assays, treat cells for 24-72 hours and assess viability by MTT. For apoptosis studies, treat with Fluphenazine (1-20 uM, 24-48 hours) and stain with Annexin V/PI for flow cytometry. For receptor internalization studies, use fluorescently labeled Fluphenazine-d8 (e.g., FITC conjugate) and visualize by confocal microscopy after treatment at 37degC for 0-60 minutes. For metabolism studies, treat liver microsomes or hepatocytes with Fluphenazine-d8 (1-10 uM) for 0-60 minutes, extract metabolites, and analyze by LC-MS/MS to identify metabolic pathways. The d8 label allows tracking of the parent compound and its metabolites.
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| Animal Protocol |
Animal studies are not performed with Fluphenazine-d8 as the labeled compound is used as an internal standard. For PK studies of Fluphenazine, administer unlabeled Fluphenazine dihydrochloride to rats via intramuscular (depot) injection (0.1-1 mg/kg) or oral administration (1-5 mg/kg). Collect blood at multiple time points (0-72 hours). Harvest plasma, add Fluphenazine-d8 dihydrochloride as internal standard, perform liquid-liquid extraction (e.g., with ethyl acetate or hexane), and analyze by LC-MS/MS. Calculate PK parameters: Cmax, Tmax, t1/2, AUC, clearance (CL), and volume of distribution (Vd). For tissue distribution studies, sacrifice animals at selected time points, harvest brain, liver, kidney, and heart, homogenize, and analyze as above. For pharmacodynamic studies, use the conditioned avoidance response (CAR) test in rats or the apomorphine-induced climbing test in mice to assess antipsychotic activity. Administer Fluphenazine (0.1-1 mg/kg s.c. or i.p.) and measure behavioral responses. Use Fluphenazine-d8 as analytical standard for correlating brain and plasma drug concentrations with behavioral effects. For catalepsy studies (measure of extrapyramidal side effects), administer Fluphenazine (0.5-2 mg/kg i.p.) and measure the time an animal remains immobile with both forepaws placed on a horizontal bar.
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| ADME/Pharmacokinetics |
Fluphenazine-d8 dihydrochloride has a molecular weight of 518.49 and formula C22H20D8Cl2F3N3OS. The deuterated form is an analytical standard. Fluphenazine itself has a long elimination half-life (approximately 15-30 hours after intramuscular depot injection, 10-20 hours after oral administration). It is highly lipophilic and extensively distributed into tissues, with a large volume of distribution (>20 L/kg). Fluphenazine is metabolized primarily by CYP2D6 and other CYPs, with metabolites excreted in urine and feces. The d8 label shifts the mass by 8 Da, enabling use as an internal standard. Solubility: water-soluble. Storage: powder at -20degC (3 years), 4degC (2 years); in solvent at -80degC (6 months) or -20degC (1 month). Protect from light and moisture. The compound is stable under recommended storage conditions.
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| Toxicity/Toxicokinetics |
Fluphenazine dihydrochloride (unlabeled) has a well-characterized toxicity profile in humans. Common adverse effects include extrapyramidal symptoms (parkinsonism, akathisia, dystonia, tardive dyskinesia), sedation, orthostatic hypotension, anticholinergic effects (dry mouth, constipation, blurred vision), and neuroleptic malignant syndrome (rare but serious). Chronic use can cause hyperprolactinemia (galactorrhea, amenorrhea). Hepatotoxicity and agranulocytosis are rare. The deuterated form (d8) is not intended for in vivo administration as a therapeutic. As an analytical standard, it is considered safe for laboratory use under standard chemical safety guidelines. Standard laboratory precautions (gloves, lab coat, safety glasses) should be used. The compound is a phenothiazine derivative; avoid inhalation, ingestion, and skin contact. Dispose of waste according to institutional guidelines for controlled substances. In case of accidental exposure, wash affected area with soap and water. If ingested, seek medical attention. Use appropriate containment and handling procedures.
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| References |
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Trzeciak HI, et al. Behavioral effects of withdrawal of fluphenazine after long-term treatment. Arzneimittelforschung. 1976;26(9):1697-700. [3]. Whelpton R, Curry SH. Effect of 20, 6Methods for study of fluphenazine kinetics in man. J Pharm Pharmacol. 1976 Dec;28(12):869-73. [4]. Javaid JI, et al. Fluphenazine determination in human plasma by a sensitive gas chromatographic method using nitrogen detector. J Chromatogr Sci. 1981 Sep;19(9):439-43. |
| Additional Infomation |
Fluphenazine-d8 dihydrochloride is a stable isotope-labeled compound used as an internal standard for the quantification of Fluphenazine and its metabolites by LC-MS/MS in pharmacokinetic studies and therapeutic drug monitoring. Fluphenazine (brand names: Prolixin, Permitil) is a typical antipsychotic of the phenothiazine class used for the treatment of schizophrenia and other psychotic disorders. It is available as oral tablets, oral solution, and long-acting depot injection (fluphenazine decanoate). The dihydrochloride salt is the water-soluble form used for oral administration. The d8 label contains eight deuterium atoms, providing a mass shift of 8 Da for accurate quantification. The compound is for research use only and not for diagnostic or therapeutic applications.
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| Molecular Formula |
C22H20D8CL2F3N3OS
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|---|---|
| Molecular Weight |
518.49
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| Related CAS # |
Fluphenazine dihydrochloride;146-56-5
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| Appearance |
Typically exists as solid at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9287 mL | 9.6434 mL | 19.2868 mL | |
| 5 mM | 0.3857 mL | 1.9287 mL | 3.8574 mL | |
| 10 mM | 0.1929 mL | 0.9643 mL | 1.9287 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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