| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Dopamine D4 receptors (D4DR) and serotonin 5-HT2A receptors. Clozapine binds preferentially to D4 and 5-HT2 receptors (Ki for 5-HT2A ~1.4 nM, D4 ~9 nM) and acts as a weak D1 and D2 antagonist. It also binds to 5-HT6 and 5-HT7 receptors and the muscarinic M1 receptor (Ki 9.5 nM).
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
Clozapine-d8 has the same receptor binding profile as unlabeled clozapine. Clozapine is a potent antagonist at dopamine D4 and serotonin 5-HT2A receptors, with weaker activity at D1 and D2 receptors. This unique receptor profile contributes to its efficacy in treatment-resistant schizophrenia. |
| ln Vivo |
Unlabeled clozapine is a gold-standard antipsychotic for treatment-resistant schizophrenia. It reduces positive and negative symptoms and decreases the risk of suicide. Clozapine-d8 is not administered therapeutically but is used as an internal standard for therapeutic drug monitoring and PK studies.
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| Enzyme Assay |
Membrane preparations from CHO or HEK293 cells expressing human dopamine D4 or serotonin 5-HT2A receptors (5-20 microg) are incubated with Clozapine-d8 (0.01-1000 nM) and a radioligand (e.g., [3H]spiperone for D2-like, [3H]ketanserin for 5-HT2A) in binding buffer (50 mM Tris-HCl, pH 7.4, 5 mM MgCl2, 1 mM EDTA, 0.1% BSA) at 25degC for 60-90 minutes. Nonspecific binding is determined with 10 microM haloperidol or ketanserin.
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| Cell Assay |
Cells expressing dopamine or serotonin receptors (e.g., HEK293-D4, CHO-5-HT2A) are treated with Clozapine-d8 (0.1-1000 nM) for 30-60 minutes. Functional activity (cAMP accumulation for D4; IP accumulation for 5-HT2A) is measured using HTRF (cAMP HiRange) or IP-One kits to distinguish agonist vs. antagonist activity.
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| Animal Protocol |
Not applicable for internal standard. For PK studies, rats or dogs are administered unlabeled clozapine (1-10 mg/kg, oral or IV). Blood samples are collected at multiple time points (0.5-48 hours), plasma is spiked with Clozapine-d8 as an internal standard, and clozapine and its major metabolite (norclozapine) are quantified by LC-MS/MS.
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| ADME/Pharmacokinetics |
Clozapine has an oral bioavailability of 50-60% in humans, with a plasma half-life of 12-16 hours (range 6-33 hours). It is extensively metabolized in the liver by CYP1A2, CYP2D6, CYP3A4, and flavin-containing monooxygenase 3 (FMO3). Clozapine-d8 has identical PK properties.
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| Toxicity/Toxicokinetics |
Clozapine is associated with significant toxicities, including agranulocytosis (0.8-1.5% incidence, requiring regular blood monitoring), myocarditis (1-3%), seizures (1-5%), and metabolic syndrome. The d8-labeled version is safe at tracer levels in research settings. Handle unlabeled clozapine with extreme care.
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| References | |
| Additional Infomation |
Clozapine-d8 is for research use only as an analytical standard, not for human administration. Unlabeled clozapine (Clozaril®) is FDA-approved for treatment-resistant schizophrenia. The d8-labeled version is essential for LC-MS/MS-based therapeutic drug monitoring (TDM) to ensure safe and effective dosing of clozapine in psychiatric patients.
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| Molecular Formula |
C18H19CLN4
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|---|---|
| Molecular Weight |
334.872555971146
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| Exact Mass |
334.18
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| CAS # |
1185053-50-2
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| Related CAS # |
Clozapine;5786-21-0;Clozapine-d4;204395-52-8
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| PubChem CID |
135858214
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
489.2±55.0 °C at 760 mmHg
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| Flash Point |
249.6±31.5 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.681
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| LogP |
2.36
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
23
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| Complexity |
446
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C1(C(N(C(C(N1C)([2H])[2H])([2H])[2H])C2=NC3=C(C=CC(=C3)Cl)NC4=CC=CC=C42)([2H])[2H])[2H]
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| InChi Key |
QZUDBNBUXVUHMW-JNJBWJDISA-N
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| InChi Code |
InChI=1S/C18H19ClN4/c1-22-8-10-23(11-9-22)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3/i8D2,9D2,10D2,11D2
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| Chemical Name |
3-chloro-6-(2,2,3,3,5,5,6,6-octadeuterio-4-methylpiperazin-1-yl)-11H-benzo[b][1,4]benzodiazepine
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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 | 2.9862 mL | 14.9312 mL | 29.8623 mL | |
| 5 mM | 0.5972 mL | 2.9862 mL | 5.9725 mL | |
| 10 mM | 0.2986 mL | 1.4931 mL | 2.9862 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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