| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
(Z)-Flunarizine targets voltage-gated T-type calcium channels and voltage-gated sodium channels as a dual blocker. The parent compound flunarizine is a fluorinated derivative of cinnarizine and a D2 dopamine receptor antagonist with anticonvulsant and antimigraine activities. It blocks calcium influx through T-type channels in vascular smooth muscle and neuronal tissues, leading to peripheral and cerebral vasodilation. The Z-isomer is pharmacologically similar but is used as an analytical reference for impurity testing. This compound also has activity at D2 dopamine receptors as an antagonist, contributing to its antiemetic and antimigraine effects [14L11-L13][15L22-L24].
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| ln Vitro |
No in vitro activity data has been specifically characterized for (Z)-Flunarizine as a stand-alone isomer. The parent compound flunarizine has well-documented in vitro activity: it inhibits T-type calcium channels with IC50 values in the low micromolar range (1-10 microM) in neuronal and vascular smooth muscle cell preparations. It also blocks Na+ channels, contributing to its anticonvulsant activity. In D2 dopamine receptor binding assays using rat striatal membranes, flunarizine has Ki values of approximately 10-50 nM. The Z-isomer is expected to have similar pharmacological activity, but no specific IC50 values are reported for this impurity [14L11-L12][15L22-L23].
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| ln Vivo |
No in vivo activity data is available for (Z)-Flunarizine as a pure compound. The parent compound flunarizine is an approved drug for the prophylaxis of migraine, vestibular vertigo, and as a vasodilator for peripheral circulatory disorders. In animal models, flunarizine (10-40 mg/kg oral) reduces electrically induced cortical spreading depression, a model of migraine aura. It also reduces seizure severity in pentylenetetrazole-induced seizure models. The Z-isomer, as an impurity present at trace levels (<0.1%) in flunarizine drug products, is not expected to contribute to efficacy or toxicity. No dedicated in vivo studies have been performed [2L23-L25].
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| Enzyme Assay |
Not applicable for biological assays as this compound is an analytical impurity standard, not a drug candidate. For non-cellular analytical characterization, dissolve (Z)-Flunarizine in methanol to 0.5 mg/mL. Analyze by reverse-phase HPLC (C18 column, 250×4.6 mm, 5 microm) with mobile phase: 0.1% TFA in water (A) and acetonitrile (B) in gradient elution (30-80% B over 30 min). Flow rate 1.0 mL/min, UV detection at 254 nm. The Z-isomer elutes separately from the E-isomer, allowing quantification. For forced degradation studies, expose flunarizine drug substance to UV light (365 nm) to induce isomerization and generate the Z-isomer. Identify by LC-MS/MS (positive ion mode, m/z 405 [M+H]+). Retention time ~12-15 min. System suitability requires resolution >2.0 from flunarizine main peak [13L23-L25].
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| Cell Assay |
No cell-based biological assays are performed with (Z)-Flunarizine as it is not a drug candidate. For impurity profiling in flunarizine drug substance for quality control: prepare flunarizine sample at 1 mg/mL in mobile phase. Separate isomers using chiral HPLC or normal-phase chromatography. (Z)-Flunarizine is used as a reference standard at 0.05-0.5% spiking levels to verify the specificity of the analytical method. Determine limit of detection (LOD) based on signal-to-noise ratio (S/N ≥3). Typical acceptance criteria for EP Impurity D in flunarizine drug substance: ≤0.10% by area normalization. Calibration range: 0.02-1.0 microg/mL. Forced isomerization studies: expose flunarizine to light and monitor Z-isomer formation over time [13L25].
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| Animal Protocol |
Not applicable for animal studies. For pharmaceutical development, (Z)-Flunarizine is used exclusively as an analytical reference standard and is not administered to animals. Flunarizine itself has undergone extensive preclinical testing in rats, dogs, and monkeys. In rat toxicology studies, flunarizine doses up to 40 mg/kg/day for 13 weeks showed CNS depression, weight gain reduction, and fatty infiltration of the liver. The Z-isomer is not studied as a single entity. For analytical method validation, reference standards are used without animal dosing. Storage: -20degC powder under inert atmosphere; protect from light. For research use only-not for human consumption [13L25-L26].
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| ADME/Pharmacokinetics |
No pharmacokinetic data exists for (Z)-Flunarizine as a pure isomer. The parent compound flunarizine, when administered orally, has a bioavailability of ~60-80%, reaches Cmax at 2-4 h (Tmax), is highly protein bound (>95%), and has a very long terminal half-life (t½) of 2-3 weeks in humans due to high tissue distribution (Vd ~20-30 L/kg). It is extensively metabolized by CYP2D6 to inactive metabolites. The Z-isomer, if present as an impurity at trace levels, would follow similar PK behavior but is not quantifiable in systemic circulation. The compound is for analytical research use only and not intended for in vivo administration [2L8-L10][2L23-L25].
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| Toxicity/Toxicokinetics |
No toxicity data is available for (Z)-Flunarizine as a stand-alone compound. In flunarizine drug substance, the Z-isomer is controlled as an impurity (EP Impurity D) with a typical acceptance limit of ≤0.10%. The parent flunarizine has a well-characterized safety profile: common adverse effects include weight gain, sedation, depression, and extrapyramidal symptoms (tremor, rigidity) with long-term use. Rare but serious effects: parkinsonism and tardive dyskinesia. (Z)-Flunarizine is not known to be genotoxic or carcinogenic. Standard handling precautions: avoid inhalation, ingestion, skin/eye contact. Use PPE (gloves, lab coat, goggles) in a fume hood. Storage: -20degC, protected from light. For research use only [13L25-L29].
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| References | |
| Additional Infomation |
(Z)-Flunarizine is also known as Flunarizine EP Impurity D, Flunarizine Impurity 4, and (Z)-1-[bis(4-fluorophenyl)methyl]-4-(cinnamyl)piperazine. CAS: 693765-11-6. Molecular formula C26H26F2N2, MW 404.49. Boiling point: 511.3+/-50.0degC (predicted). Density: 1.170+/-0.06 g/cm3. pKa: 6.99+/-0.10. Appearance: colorless to yellow thick oil. Solubility: DMSO (slightly), methanol (slightly), chloroform (slightly). Storage: amber vial, inert atmosphere, -20degC. For research use only-not for human diagnostic or therapeutic use. Purity typically >95% [13L23-L25][14L17-L21].
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| Molecular Formula |
C26H26F2N2
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|---|---|
| Molecular Weight |
404.49
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| Exact Mass |
404.206
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| CAS # |
693765-11-6
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| PubChem CID |
1711971
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
487
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CN(CCN1C/C=C\\C2=CC=CC=C2)C(C3=CC=C(C=C3)F)C4=CC=C(C=C4)F
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| InChi Key |
SMANXXCATUTDDT-DAXSKMNVSA-N
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| InChi Code |
InChI=1S/C26H26F2N2/c27-24-12-8-22(9-13-24)26(23-10-14-25(28)15-11-23)30-19-17-29(18-20-30)16-4-7-21-5-2-1-3-6-21/h1-15,26H,16-20H2/b7-4-
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| Chemical Name |
1-[bis(4-fluorophenyl)methyl]-4-[(Z)-3-phenylprop-2-enyl]piperazine
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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 | 2.4722 mL | 12.3612 mL | 24.7225 mL | |
| 5 mM | 0.4944 mL | 2.4722 mL | 4.9445 mL | |
| 10 mM | 0.2472 mL | 1.2361 mL | 2.4722 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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