| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
The primary targets of N,N,O-Tridesmethylvenlafaxine are the serotonin transporter (SERT) and norepinephrine transporter (NET), which are the same targets as its parent drug venlafaxine. However, the metabolite has significantly reduced affinity for these transporters compared to venlafaxine and its primary active metabolite O-desmethylvenlafaxine. The compound may also interact with other monoamine transporters and receptors, though its pharmacological activity is considerably weaker than that of the parent compound. As an endogenous metabolite, it may have additional, as-yet-unidentified physiological functions within the body. These characteristics make it relevant for pharmacokinetic and drug metabolism studies.
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| ln Vitro |
In vitro, N,N,O-Tridesmethylvenlafaxine is studied primarily as a metabolite in drug metabolism research rather than for its own pharmacological activity. It is used as a reference standard in analytical method development for quantifying venlafaxine and its metabolites in biological samples. The compound is also employed in in vitro metabolism studies using liver microsomes or hepatocytes to investigate the enzymatic pathways involved in venlafaxine biotransformation. Its formation from venlafaxine and subsequent metabolic fate are characterized using LC-MS/MS techniques. These studies help elucidate the complete metabolic profile of venlafaxine and identify the cytochrome P450 enzymes responsible for each demethylation step.
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| ln Vivo |
In vivo, N,N,O-Tridesmethylvenlafaxine is formed as a minor metabolite following venlafaxine administration. It is excreted in urine and can be detected in plasma, serving as a marker of venlafaxine metabolism. Its concentration in biological fluids reflects the activity of metabolic enzymes and can be used to study interindividual variability in drug metabolism. The compound itself does not contribute significantly to the antidepressant effects of venlafaxine due to its low potency at SERT and NET. However, its presence provides valuable information about the completeness of venlafaxine biotransformation and potential metabolic interactions with other drugs.
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| Enzyme Assay |
In vitro enzyme/receptor binding (cell-free) assays for N,N,O-Tridesmethylvenlafaxine typically involve assessing its affinity for serotonin and norepinephrine transporters using radioligand binding techniques. The compound is incubated with membrane preparations expressing human SERT or NET and a labeled ligand (e.g., [³H]-citalopram for SERT or [³H]-nisoxetine for NET) at concentrations ranging from 0.1 nM to 100 μM. Binding affinity (Ki) is determined by competitive displacement curves. Functional assays measuring inhibition of [³H]-serotonin or [³H]-norepinephrine uptake into cells expressing the transporters are also conducted. All assays include venlafaxine and O-desmethylvenlafaxine as reference compounds for comparison of relative potency.
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| Cell Assay |
In vitro cell-based assays for N,N,O-Tridesmethylvenlafaxine are conducted using cell lines expressing human serotonin or norepinephrine transporters (e.g., HEK293 or CHO cells stably transfected with SERT or NET). Cells are seeded in 96-well plates and treated with compound concentrations ranging from 0.1 nM to 100 μM. After incubation, [³H]-serotonin or [³H]-norepinephrine uptake is measured, and IC₅₀ values are determined. Cell viability is assessed using MTT or CellTiter-Glo assays to confirm that observed effects are not due to cytotoxicity. The compound is also tested in neuronal cell lines to evaluate any potential effects on neurite outgrowth or other cellular functions. Experiments include venlafaxine as a positive control and vehicle controls.
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| Animal Protocol |
In vivo animal studies with N,N,O-Tridesmethylvenlafaxine are typically conducted as part of venlafaxine pharmacokinetic studies rather than as standalone experiments. Rodents are administered venlafaxine via oral or intravenous routes, and plasma and urine samples are collected at multiple time points. The concentrations of venlafaxine, O-desmethylvenlafaxine, and N,N,O-Tridesmethylvenlafaxine are measured using validated LC-MS/MS methods. Pharmacokinetic parameters such as AUC, Cmax, Tmax, and half-life are calculated for each analyte. These studies help define the metabolic pathways and enzyme systems involved in venlafaxine biotransformation, and assess the impact of genetic polymorphisms or drug interactions on metabolite formation.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
The known metabolites of O-demethylvenlafaxine include (2S,3S,4S,5R,6S)-6-[4-[2-amino-1-(1-hydroxycyclohexyl)ethyl]phenoxy]-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid. Pharmacokinetic properties of N,N,O-Tridesmethylvenlafaxine include its formation as a minor metabolite of venlafaxine with a relatively low plasma concentration compared to the parent drug and O-desmethylvenlafaxine. The compound is formed through sequential N-demethylation and O-demethylation reactions catalyzed by cytochrome P450 enzymes, primarily CYP2D6 and CYP3A4. It has a longer half-life than venlafaxine due to its more polar nature, which reduces renal reabsorption. The compound is primarily excreted in urine as the free metabolite or as glucuronide conjugates. Its pharmacokinetics are influenced by factors affecting CYP2D6 activity, including genetic polymorphisms and drug interactions. |
| Toxicity/Toxicokinetics |
Toxicological data for N,N,O-Tridesmethylvenlafaxine are limited, as it is a minor metabolite rather than a therapeutic agent. No significant toxicity has been attributed specifically to this metabolite at the concentrations achieved following venlafaxine administration. The compound is generally considered safe for research use at the concentrations employed in analytical and metabolism studies. However, as with all research chemicals, appropriate safety precautions should be taken during handling, including the use of personal protective equipment and adequate ventilation. Comprehensive toxicological profiling has not been conducted for this metabolite alone.
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| Additional Infomation |
N,N,O-Tridesmethylvenlafaxine is a research chemical used primarily in pharmacokinetic and drug metabolism studies. It serves as a reference standard for the quantification of venlafaxine metabolites in biological samples and for the investigation of venlafaxine biotransformation pathways. As an endogenous metabolite, it is also of interest in metabolomics research. The compound is not intended for diagnostic or therapeutic use and is available only for research purposes. It is typically supplied as a white to off-white solid powder with a purity of ≥98%.
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| Molecular Formula |
C₁₄H₂₁NO₂
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| Molecular Weight |
235.32
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| Exact Mass |
235.157
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| CAS # |
149289-29-2
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| PubChem CID |
9859500
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| Appearance |
White to off-white solid powder
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| LogP |
2.83
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
17
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| Complexity |
230
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BHCUWXACHAFFSK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H21NO2/c15-10-13(11-4-6-12(16)7-5-11)14(17)8-2-1-3-9-14/h4-7,13,16-17H,1-3,8-10,15H2
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| Chemical Name |
4-[2-amino-1-(1-hydroxycyclohexyl)ethyl]phenol
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| Synonyms |
N,N,OTridesmethylvenlafaxine N,N,O Tridesmethylvenlafaxine
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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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2495 mL | 21.2477 mL | 42.4953 mL | |
| 5 mM | 0.8499 mL | 4.2495 mL | 8.4991 mL | |
| 10 mM | 0.4250 mL | 2.1248 mL | 4.2495 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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