| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
The molecular target of Itopride N-Oxide is not well-defined, as the compound is an inactive metabolite. Its parent drug, Itopride, exerts a dual mechanism of action by acting as a dopamine D2 receptor antagonist and as an acetylcholinesterase inhibitor. This dual activity enhances gastrointestinal motility by increasing acetylcholine release. Itopride N-Oxide itself has not been reported to bind to these receptors or enzymes with significant affinity; however, it is recognized as a substrate for the xenobiotic-metabolizing enzyme FMO3, which is responsible for its formation.
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| ln Vitro |
While Itopride N-Oxide itself has no direct therapeutic activity, its parent drug, Itopride, demonstrates potent in vitro inhibition. Itopride is a competitive antagonist at the dopamine D2 receptor with an IC50 of approximately 1.1 nM. It also inhibits human erythrocyte acetylcholinesterase with an IC50 of 20.8 uM. The metabolite is not typically tested for these activities, as it is considered pharmacologically inactive. Nonetheless, its formation is a critical marker of FMO3 enzyme activity in vitro, and its concentration can be used to assess the metabolic stability of the parent drug in liver microsome assays.
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| ln Vivo |
Itopride N-Oxide does not possess direct in vivo pharmacological activity. However, its presence in plasma is a key indicator of Itopride metabolism. In vivo, following oral administration of Itopride, the parent drug is rapidly and extensively absorbed, with plasma levels peaking after 35 minutes. It is then quickly converted to the N-oxide metabolite by FMO3. The pharmacokinetic profile of Itopride N-Oxide is genotype-dependent, with significant differences observed between individuals with different FMO3 alleles. The metabolite is primarily excreted unchanged in the urine, accounting for about 75.4% of the administered dose.
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| Enzyme Assay |
The standard protocol for assessing the generation of Itopride N-Oxide involves an in vitro microsomal assay. The reaction mixture contains human liver microsomes (or recombinant FMO3 enzyme), Itopride substrate, and an NADPH-regenerating system in a potassium phosphate buffer (pH 7.4). The reaction is initiated by adding the substrate and incubated at 37degC for 30 minutes. It is terminated by adding acetonitrile with an internal standard. The mixture is centrifuged, and the supernatant is analyzed by LC-MS/MS. The rate of metabolite formation is calculated by comparing the peak area of Itopride N-Oxide to a standard curve.
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| Cell Assay |
Cellular assays are not typically used to evaluate Itopride N-Oxide directly, as it is a metabolite. However, studies often involve the incubation of Itopride with primary human hepatocytes. Cells are cultured in Williams' Medium E and treated with 1-10 uM Itopride for up to 24 hours. At various time points, cell culture supernatants are collected, and the conversion to Itopride N-Oxide is measured by LC-MS/MS. This method is used to evaluate the metabolic clearance of Itopride and the potential for drug-drug interactions affecting FMO3 activity. The results help predict in vivo pharmacokinetics.
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| Animal Protocol |
In vivo pharmacokinetic and metabolism studies of Itopride N-Oxide are conducted in healthy human volunteers or animal models such as rats or humanized-liver mice. A standard protocol involves a single oral dose of Itopride (e.g., 50 mg). Blood samples are collected at pre-dose and at multiple time points (0.25 to 24 hours post-dose). Plasma concentrations of Itopride and Itopride N-Oxide are determined by a validated HPLC-MS/MS method. Pharmacokinetic parameters, including Cmax, Tmax, AUC, and elimination half-life, are calculated using non-compartmental analysis. This protocol is essential to study the impact of FMO3 genetic polymorphisms on drug exposure.
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| ADME/Pharmacokinetics |
The pharmacokinetics of Itopride N-Oxide is directly linked to that of its parent drug, Itopride. In humans, Itopride is rapidly absorbed (Tmax ~35 min) and is extensively metabolized to the N-oxide, which becomes the predominant circulating species. The plasma concentration of Itopride N-Oxide is significantly higher than that of the parent drug. The AUC of Itopride N-Oxide has been shown to vary by over 100% depending on the FMO3 genotype. The metabolite exhibits a terminal elimination half-life of approximately 5-6 hours. The compound is primarily excreted renally, with 75.4% of a dose recovered as the N-oxide in urine.
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| Toxicity/Toxicokinetics |
The toxicity of Itopride N-Oxide is considered low, as it is an inactive metabolite of a drug with a favorable safety profile. In clinical studies, the overall incidence of adverse events with Itopride is comparable to placebo, with most events being mild and transient. Common side effects of the parent drug include diarrhea, abdominal pain, headache, and dizziness. There is no specific toxicological data for the isolated metabolite, but it is not associated with significant pharmacodynamic effects. Standard laboratory safety precautions, including gloves and lab coats, are recommended when handling the pure compound as a reference standard.
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| Additional Infomation |
Itopride N-Oxide is a critical compound for pharmaceutical quality control and regulatory science. It is used as a reference standard to validate analytical methods such as HPLC and LC-MS/MS for the quantification of Itopride and its impurities in drug substance and drug product. It is also an essential tool for studying the in vivo role of flavin-containing monooxygenase 3 (FMO3), an enzyme that is less studied than cytochrome P450s. Because FMO3 is not easily inhibited, drugs primarily metabolized by it, like Itopride, have a lower risk of drug-drug interactions, making this metabolite important for drug development. The compound is not an approved drug.
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| Molecular Formula |
C20H26N2O5
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|---|---|
| Molecular Weight |
374.43
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| Exact Mass |
374.184
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| CAS # |
141996-98-7
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| PubChem CID |
71433796
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| Appearance |
Brown to black Solid-Liquid Mixture
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| LogP |
3.183
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
27
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| Complexity |
452
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C[N+](C)(CCOC1=CC=C(C=C1)CNC(=O)C2=CC(=C(C=C2)OC)OC)[O-]
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| InChi Key |
PZXRVVNIISGQFI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H26N2O5/c1-22(2,24)11-12-27-17-8-5-15(6-9-17)14-21-20(23)16-7-10-18(25-3)19(13-16)26-4/h5-10,13H,11-12,14H2,1-4H3,(H,21,23)
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| Chemical Name |
2-[4-[[(3,4-dimethoxybenzoyl)amino]methyl]phenoxy]-N,N-dimethylethanamine oxide
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~25 mg/mL (~66.77 mM; with ultrasonication)
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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 | 2.6707 mL | 13.3536 mL | 26.7073 mL | |
| 5 mM | 0.5341 mL | 2.6707 mL | 5.3415 mL | |
| 10 mM | 0.2671 mL | 1.3354 mL | 2.6707 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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