| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
Histamine H1 Receptor and L-Type Voltage-Gated Calcium Channels (Cav1.2). Cinnarizine D8 acts as a potent H1-histamine receptor antagonist, blocking the effects of histamine, particularly in the vestibular system (balance center). It also inhibits the influx of extracellular calcium ions through L-type calcium channels in vascular smooth muscle, leading to vasodilation, particularly in cerebral and peripheral blood vessels, without significantly affecting blood pressure.
|
|---|---|
| ln Vitro |
Cinnarizine exhibits H1 receptor antagonism with a Ki of approximately 10-50 nM in radioligand binding assays using guinea pig cerebellar membranes. It inhibits calcium-induced contraction of isolated rat aortic rings (IC50 = 100-500 nM) and K+-induced depolarization in isolated basilar arteries. It also has anti-vertigo and anti-emetic effects by reducing vestibular sensory input.
|
| ln Vivo |
In animal models of motion sickness (e.g., rotating chair or cross-coupled acceleration), oral cinnarizine (10-30 mg/kg) significantly reduces emesis and behavioral signs of motion sickness in dogs, cats, and squirrel monkeys. In a rat model of cerebral ischemia (middle cerebral artery occlusion, MCAO), pre-treatment with cinnarizine (20-50 mg/kg i.p.) reduces infarct volume and improves neurological deficit scores via calcium channel blockade.
|
| Enzyme Assay |
Radioligand binding assays for H1 receptors: Membrane preparations from guinea pig cerebellum (50-100 microg protein) are incubated with [3H]mepyramine as the radioligand (1-2 nM) and varying concentrations of Cinnarizine D8 (0.1-1000 nM) in 50 mM Tris-HCl buffer (pH 7.4) for 60 min at 25degC. Nonspecific binding is determined with 10 microM pyrilamine. Bound and free radioligands are separated by filtration through GF/B filters, and bound radioactivity is counted by liquid scintillation. Ki values are calculated.
|
| Cell Assay |
Rat aortic vascular smooth muscle cells (A7r5) are cultured in DMEM with 10% FBS. Cells are seeded in 96-well plates (50,000 cells/well) for 24 h, then loaded with Fluo-4 AM (5 microM) for 60 min at 37degC. Cells are pre-incubated with varying concentrations of Cinnarizine D8 (0.1-1000 nM) for 30 min, then depolarized with 60 mM KCl to open L-type calcium channels. Intracellular calcium increases are measured by fluorescence (ex/em 494/516 nm). IC50 values for inhibition of calcium influx are calculated.
|
| Animal Protocol |
Male Sprague-Dawley rats (200-250 g) are used in a motion sickness model: animals are placed in a rotating chamber (70 rpm) on a tilt table (15deg). Before rotation, Cinnarizine D8 (5-30 mg/kg) or vehicle is administered orally 60 min prior. The number of defecations, urinations, and vomiting episodes (if species permits) are recorded. In rodents, the number of pica episodes (eating of non-nutritive substances like kaolin, a proxy for nausea) is used as a behavioral endpoint.
|
| ADME/Pharmacokinetics |
The D8-labeled compound serves as an internal standard (IS) for bioanalysis. Cinnarizine is lipophilic, well absorbed orally (bioavailability ~75%), and has a long terminal half-life (~24 h). It is >95% protein bound and extensively metabolized (CYP2D6) to N-dealkylated metabolites, with negligible renal excretion of unchanged drug. The D8 isotopologue has identical chromatographic retention and ionization, making it ideal for LC-MS quantification.
|
| Toxicity/Toxicokinetics |
The D8-labeled version is for research use only and is not administered to humans. Cinnarizine has a favorable safety profile; common AEs include drowsiness (somnolence, 5-15%), weight gain (due to increased appetite), dry mouth, and gastrointestinal upset (dyspepsia, nausea). Extrapyramidal symptoms (tremors, rigidity, parkinsonism) are rare but may occur with prolonged use in elderly patients.
|
| Additional Infomation |
Cinnarizine (Stugeron) is available in Europe and other regions (but not FDA-approved in the US). It is indicated for motion sickness, vertigo (Meniere‘s disease, labyrinthitis), nausea, vomiting, and tinnitus. Cinnarizine D8 is a research internal standard used for LC-MS/MS pharmacokinetic studies, bioequivalence trials, and therapeutic drug monitoring (TDM), particularly to study its long half-life and accumulation during chronic dosing.
|
| Molecular Formula |
C26H28N2
|
|---|---|
| Molecular Weight |
368.51392
|
| Exact Mass |
376.275
|
| CAS # |
1185242-27-6
|
| Related CAS # |
Cinnarizine;298-57-7
|
| PubChem CID |
45038684
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
4.982
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
28
|
| Complexity |
429
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
[2H]C1(C(N(C(C(N1C/C=C/C2=CC=CC=C2)([2H])[2H])([2H])[2H])C(C3=CC=CC=C3)C4=CC=CC=C4)([2H])[2H])[2H]
|
| InChi Key |
DERZBLKQOCDDDZ-RVEWZOGKSA-N
|
| InChi Code |
InChI=1S/C26H28N2/c1-4-11-23(12-5-1)13-10-18-27-19-21-28(22-20-27)26(24-14-6-2-7-15-24)25-16-8-3-9-17-25/h1-17,26H,18-22H2/b13-10+/i19D2,20D2,21D2,22D2
|
| Chemical Name |
1-benzhydryl-2,2,3,3,5,5,6,6-octadeuterio-4-[(E)-3-phenylprop-2-enyl]piperazine
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 2.7136 mL | 13.5682 mL | 27.1363 mL | |
| 5 mM | 0.5427 mL | 2.7136 mL | 5.4273 mL | |
| 10 mM | 0.2714 mL | 1.3568 mL | 2.7136 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
