| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
Carbamazepine 10,11-epoxide targets sodium channels, modulating them to stabilize neuronal membranes. Although the exact mechanism of action of carbamazepine-10,11-epoxide remains incompletely elucidated, it is hypothesized to exert its effects by inhibiting sodium channels. By blocking voltage-gated sodium channels, CBZ-E reduces the repetitive firing of action potentials in neurons, which is the basis of its anticonvulsant activity. The compound is equipotent with carbamazepine as an anticonvulsant, indicating that it contributes significantly to the therapeutic effects of carbamazepine therapy. In addition to sodium channel modulation, CBZ-E may also affect other targets, including calcium channels and neurotransmitter systems, although these effects are less well characterized. The compound's epoxide structure makes it reactive and potentially capable of forming covalent adducts with proteins, which may contribute to its toxicity and drug interaction profile. CBZ-E is formed via cytochrome P450 (CYP)-mediated oxidation in the liver, primarily by CYP3A4 and CYP2C8. The compound is further metabolized to the inactive diol metabolite by epoxide hydrolase, which is an important detoxification pathway. Inhibition or genetic variation in epoxide hydrolase can lead to accumulation of CBZ-E and increased risk of toxicity.
|
|---|---|
| ln Vitro |
In vitro, carbamazepine 10,11-epoxide exhibits anticonvulsant activity. It is formed from carbamazepine by cytochrome P450 isoforms CYP3A4 and CYP2C8 in the liver, as demonstrated using HepG2 cells expressing CYP3A4 or CYP2C8. The compound has been found to decompose in gastric juice in vitro. In vitro studies have also investigated the compound's potential role in drug interactions and toxicity, particularly in relation to its metabolic pathways. The compound's epoxide nature makes it reactive and capable of forming adducts with proteins, which has been studied in in vitro systems. In enzyme inhibition studies, CBZ-E has been shown to inhibit various cytochrome P450 enzymes, potentially leading to drug-drug interactions. The compound's anticonvulsant activity has been demonstrated in vitro using electrophysiological recordings from neuronal preparations. In studies of drug metabolism, CBZ-E is used as a standard to quantify the formation of the metabolite from carbamazepine in liver microsomes and hepatocyte cultures. The compound's stability in various media has been characterized, with decomposition observed in gastric juice in vitro.
|
| ln Vivo |
In vivo, carbamazepine 10,11-epoxide has anticonvulsant activity against maximal electroshock-induced seizures in mice. In animal studies, the compound is rapidly formed after carbamazepine administration and reaches plasma concentrations higher than those of the parent compound in dogs. The compound is an orally bioactive metabolite of carbamazepine. In humans, CBZ-E contributes to the anticonvulsant effects of carbamazepine therapy. The compound's accumulation can occur when epoxide hydrolase activity is inhibited, leading to increased risk of toxicity. In vivo studies have investigated the pharmacokinetics of CBZ-E, showing that it is rapidly formed and eliminated. The compound has been found in wastewater effluent, indicating its environmental presence. In clinical studies, monitoring of CBZ-E levels is important for optimizing carbamazepine therapy and minimizing toxicity. The compound's anticonvulsant activity in animal models supports its role as an active metabolite. Its pharmacokinetic profile, including rapid formation and elimination, has been characterized in various species.
|
| Enzyme Assay |
In vitro enzyme assays for carbamazepine 10,11-epoxide typically involve the use of liver microsomes or recombinant CYP enzymes to study its formation from carbamazepine. A typical assay protocol involves incubating carbamazepine (10-100 μM) with human liver microsomes (0.5-1.0 mg/mL) or recombinant CYP3A4 or CYP2C8 in the presence of an NADPH-generating system (e.g., NADPH, glucose-6-phosphate, glucose-6-phosphate dehydrogenase) in phosphate buffer (pH 7.4) at 37°C for 30-60 minutes. The reaction is terminated by the addition of ice-cold acetonitrile or methanol, and the samples are centrifuged to remove protein. The supernatant is then analyzed by HPLC or LC-MS/MS to quantify the formation of CBZ-E. For inhibition studies, potential inhibitors are co-incubated with the enzyme and substrate, and the inhibition of CBZ-E formation is assessed. For epoxide hydrolase assays, CBZ-E is used as a substrate to measure the activity of epoxide hydrolase, which converts CBZ-E to the inactive diol metabolite. In these assays, CBZ-E (10-100 μM) is incubated with liver microsomes or purified epoxide hydrolase in buffer (pH 7.4) at 37°C, and the formation of the diol metabolite is measured by HPLC or LC-MS/MS. The compound's stability in various media can be assessed by incubating CBZ-E in buffer, plasma, or gastric juice and measuring its degradation over time.
|
| Cell Assay |
In vitro cell-based assays for carbamazepine 10,11-epoxide are performed using hepatocyte or neuronal cell cultures. For studies of CBZ-E formation, HepG2 cells expressing CYP3A4 or CYP2C8 are cultured in appropriate medium and treated with carbamazepine (10-100 μM) for 24-48 hours. Culture media are collected, and the formation of CBZ-E is measured by LC-MS/MS. For studies of CBZ-E toxicity, neuronal cells (e.g., SH-SY5Y) or hepatocytes are treated with CBZ-E at various concentrations (typically 1-100 μM) for 24-72 hours. Cell viability is assessed using MTT or LDH assays. Markers of oxidative stress, apoptosis, and DNA damage are measured to assess the compound's toxic effects. For studies of drug interactions, cells are treated with CBZ-E in combination with other drugs, and the effects on cell viability and metabolism are assessed. Each experiment includes appropriate controls (untreated cells, vehicle controls, and positive controls) and is performed in triplicate to ensure statistical reliability. The compound is typically dissolved in DMSO as a stock solution and diluted in culture medium to the desired final concentration, with the final DMSO concentration kept below 0.1% to avoid solvent effects.
|
| Animal Protocol |
In vivo animal experiments with carbamazepine 10,11-epoxide are conducted in mouse or rat models of seizures. Typically, 8-12 week old male or female mice are used, and the compound is administered via intraperitoneal injection or oral gavage at doses ranging from 10-100 mg/kg. The maximal electroshock (MES) test is the standard model for assessing anticonvulsant activity. In this test, animals receive an electric shock (typically 50 mA, 0.2 sec) via corneal electrodes, and the presence or absence of hindlimb tonic extension is recorded. CBZ-E is administered 30-60 minutes before the MES test, and the percentage of animals protected from seizures is determined. For pharmacokinetic studies, blood samples are collected at various time points (typically 0, 0.5, 1, 2, 4, 8, 12, 24 hours) after compound administration, and plasma concentrations of CBZ-E are measured by LC-MS/MS. In dogs, CBZ-E is rapidly formed after carbamazepine administration and reaches plasma concentrations higher than those of the parent compound. All animal procedures are conducted in accordance with institutional animal care and use committee guidelines, with appropriate sample sizes (typically n=6-10 per group) to ensure statistical power. The compound is formulated for administration using appropriate vehicles such as saline, DMSO/PEG mixtures, or other biocompatible solvents. Endpoints include seizure protection, pharmacokinetic parameters, and histopathological examination of tissues.
|
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Carbamazepine 10,11-epoxide is a known metabolite of carbamazepine in the human body. The pharmacokinetic properties of carbamazepine 10,11-epoxide are characterized by rapid formation and elimination. Following carbamazepine administration, CBZ-E is rapidly formed in the liver by CYP3A4 and CYP2C8. In dogs, CBZ-E reaches plasma concentrations higher than those of the parent compound, indicating extensive metabolism. The compound is further metabolized to the inactive diol metabolite by epoxide hydrolase, which is an important detoxification pathway. The elimination half-life of CBZ-E is typically shorter than that of carbamazepine, reflecting its rapid clearance. The compound's pharmacokinetics can be influenced by genetic variation in CYP enzymes and epoxide hydrolase, as well as by drug interactions that inhibit or induce these enzymes. Inhibition of epoxide hydrolase can lead to accumulation of CBZ-E and increased risk of toxicity. The compound has been found to decompose in gastric juice in vitro, which may affect its oral bioavailability. In clinical practice, monitoring of CBZ-E levels is important for optimizing carbamazepine therapy and minimizing toxicity. The compound's pharmacokinetic profile makes it an important consideration in the management of patients taking carbamazepine. |
| Toxicity/Toxicokinetics |
The toxicological profile of carbamazepine 10,11-epoxide is primarily related to its epoxide nature, which makes it reactive and capable of forming covalent adducts with proteins. This reactivity may contribute to the toxicity of carbamazepine, including hypersensitivity reactions, hepatotoxicity, and teratogenicity. The compound has been studied for its potential role in drug interactions and toxicity, particularly in relation to its metabolic pathways. Inhibition of epoxide hydrolase can lead to accumulation of CBZ-E and increased risk of toxicity. In vitro studies have shown that CBZ-E can form adducts with proteins and may cause oxidative stress and apoptosis in cells. In animal studies, high doses of CBZ-E have been associated with neurotoxicity and hepatotoxicity. The compound is classified as a research chemical and is not approved for human use. Standard safety precautions should be observed when handling the compound, including the use of appropriate personal protective equipment. As with all chemicals, ingestion, inhalation, and skin contact should be avoided. The compound should be stored in a cool, dry place, away from light and moisture. The absence of reported severe adverse effects at therapeutic concentrations suggests that CBZ-E is relatively safe when formed endogenously from carbamazepine, but its accumulation can lead to toxicity.
|
| References | |
| Additional Infomation |
Carbamazepine-10,11-epoxide is the epoxide and metabolite of carbamazepine. It is a marine xenobiotic metabolite, a drug metabolite, and an allergen. It is an epoxide belonging to the urea and dibenzodiazepine classes. Its function is related to carbamazepine.
Carbamazepine 10,11-epoxide is an important compound for studying the pharmacology and toxicology of carbamazepine therapy. It is the primary pharmacologically active metabolite of the anticonvulsant drug carbamazepine. The compound exhibits anticonvulsant properties and is believed to modulate sodium channels, thereby stabilizing neuronal membranes. It is formed via cytochrome P450 (CYP)-mediated oxidation in the liver, primarily by CYP3A4 and CYP2C8. CBZ-E has been studied for its potential role in drug interactions and toxicity, particularly in relation to its metabolic pathways. The compound is equipotent with carbamazepine as an anticonvulsant and has been found in wastewater effluent. It has anticonvulsant activity against maximal electroshock-induced seizures in mice. CBZ-E is an orally bioactive metabolite of carbamazepine. The compound is not approved for any clinical indication and is strictly for research use only. Its role as an active metabolite makes it an important compound for understanding drug metabolism, drug-drug interactions, and the therapeutic and toxic effects of carbamazepine therapy. Monitoring of CBZ-E levels is important for optimizing carbamazepine therapy and minimizing toxicity. |
| Molecular Formula |
C15H12N2O2
|
|---|---|
| Molecular Weight |
252.27
|
| Exact Mass |
252.09
|
| CAS # |
36507-30-9
|
| Related CAS # |
Carbamazepine 10,11 epoxide-d10;1219804-16-6;Carbamazepine 10,11 epoxide-d2;1185025-41-5;Carbamazepine 10,11-epoxide-13C,d2;1189497-48-0;Carbamazepine 10,11-epoxide-13C,15N;122842-78-8;Carbamazepine 10,11-epoxide-13C;67411-80-7;Carbamazepine 10,11-epoxide-13C-1;1374855-73-8
|
| PubChem CID |
2555
|
| Appearance |
Off-white to light yellow solid powder
|
| Density |
1.377g/cm3
|
| Boiling Point |
390.2ºC at 760mmHg
|
| Melting Point |
204-206ºC
|
| Flash Point |
189.8ºC
|
| Index of Refraction |
1.686
|
| LogP |
3.794
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
0
|
| Heavy Atom Count |
19
|
| Complexity |
358
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC=C2C(=C1)C3C(O3)C4=CC=CC=C4N2C(=O)N
|
| InChi Key |
ZRWWEEVEIOGMMT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C15H12N2O2/c16-15(18)17-11-7-3-1-5-9(11)13-14(19-13)10-6-2-4-8-12(10)17/h1-8,13-14H,(H2,16,18)
|
| Chemical Name |
3-oxa-11-azatetracyclo[10.4.0.02,4.05,10]hexadeca-1(16),5,7,9,12,14-hexaene-11-carboxamide
|
| 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) |
DMSO: 125 mg/mL (495.50 mM)
|
|---|---|
| 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 | 3.9640 mL | 19.8200 mL | 39.6401 mL | |
| 5 mM | 0.7928 mL | 3.9640 mL | 7.9280 mL | |
| 10 mM | 0.3964 mL | 1.9820 mL | 3.9640 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
