| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Noradrenaline Transporter (NET), Serotonin Transporter (SERT), and Dopamine Transporter (DAT). 4-Hydroxyatomoxetine functions as a potent and selective norepinephrine reuptake inhibitor (NRI) by binding to the presynaptic NET and blocking the reuptake of norepinephrine, thereby increasing noradrenergic tone in the prefrontal cortex, which improves attention and reduces impulsivity and hyperactivity.
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| ln Vitro |
Atomoxetine (the parent drug) inhibits radioligand binding to human NET, SERT, and DAT with Ki values of 5 nM, 77 nM, and 1451 nM, respectively. The equipotent metabolite 4-Hydroxyatomoxetine maintains similar NET binding affinity and selectivity over SERT and DAT. The metabolite also undergoes rapid glucuronidation to 4-HAT-O-glucuronide.
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| ln Vivo |
Atomoxetine (0.3-3 mg/kg i.p.) increases extracellular norepinephrine and dopamine levels in the prefrontal cortex by 200-300% in microdialysis studies. The equipotent metabolite 4-Hydroxyatomoxetine is expected to contribute similarly to the in vivo pharmacological effect in extensive metabolizers, although it undergoes rapid glucuronidation, which limits its free plasma concentration.
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| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from HEK-293 cells expressing human NET. Membranes (20-50 microg protein) are incubated with [3H]nisoxetine (1-2 nM) and varying concentrations of 4-Hydroxyatomoxetine in 50 mM Tris-HCl buffer (pH 7.4) containing 120 mM NaCl and 5 mM KCl for 60 min at 4degC. Nonspecific binding is determined using 10 microM desipramine. Bound radioactivity is separated by GF/B filter filtration and counted by liquid scintillation. Ki values are calculated.
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| Cell Assay |
HEK-293 cells stably expressing human NET are seeded in 96-well plates and cultured for 24h. Cells are pre-incubated with various concentrations of 4-Hydroxyatomoxetine in Krebs-HEPES buffer (pH 7.4) for 10 min, followed by addition of [3H]norepinephrine (100 nM) for another 10 min at 37degC. Uptake is terminated by rapid washing with cold buffer, cells are lysed, and accumulated radioactivity is quantified by liquid scintillation. IC50 for inhibition of NE uptake is calculated.
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| Animal Protocol |
Male Sprague-Dawley rats (250-300 g) are implanted with a microdialysis probe targeting the prefrontal cortex. After 24-48 h recovery, aCSF is perfused at 1.5 microL/min and samples are collected every 20 min. After baseline stabilization (3-4 samples), atomoxetine (1-10 mg/kg i.p.) or its metabolite 4-hydroxyatomoxetine is administered, and dialysates are analyzed for norepinephrine and dopamine by HPLC-ECD. Changes are expressed as % of baseline.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
Known metabolites of 4-hydroxy-(S)-atomoxetine include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[3-methyl-4-[(1R)-3-(methylamino)-1-phenylpropoxy]phenoxy]oxacyclohexane-2-carboxylic acid. 4-hydroxy-(S)-atomoxetine is a known metabolite of (S)-atomoxetine. 4-Hydroxyatomoxetine is the primary active metabolite of atomoxetine, formed by CYP2D6. In extensive metabolizers (EMs), atomoxetine has an oral bioavailability of ~63-94% and a short half-life of ~4-5 h, whereas poor metabolizers (PMs) have a half-life of ~21 h. The metabolite undergoes rapid glucuronidation by UGT1A9 and UGT2B15 to an inactive glucuronide, and it is excreted in urine. |
| Toxicity/Toxicokinetics |
Atomoxetine carries a boxed warning for suicidal ideation in children and adolescents. Common adverse effects: GI distress (nausea, vomiting, decreased appetite), dry mouth, insomnia, fatigue, dizziness, and mild cardiovascular effects (increased HR/BP). Hepatotoxicity is rare but severe. 4-Hydroxyatomoxetine is not intended for human therapeutic use.
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| References | |
| Additional Infomation |
4-Hydroxyatormoxine is an aromatic ether and belongs to the class of phenolic compounds.
4-Hydroxyatomoxetine is a research standard for bioanalytical LC-MS/MS quantification of atomoxetine and its metabolites, particularly for therapeutic drug monitoring (TDM) and pharmacogenetic studies investigating CYP2D6 polymorphism, given that PMs have significantly higher exposure and a different AE profile compared to EMs. |
| Molecular Formula |
C₁₇H₂₁NO₂
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|---|---|
| Molecular Weight |
271.35
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| Exact Mass |
271.157
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| CAS # |
435293-66-6
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| Related CAS # |
4-Hydroxyatomoxetine-d3;1217686-14-0
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| PubChem CID |
9816910
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| Appearance |
Off-white to yellow solid powder
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| LogP |
3.821
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
20
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| Complexity |
266
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C=CC(=C1)O)O[C@H](CCNC)C2=CC=CC=C2
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| InChi Key |
PPXQPRLGNSJNJM-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C17H21NO2/c1-13-12-15(19)8-9-16(13)20-17(10-11-18-2)14-6-4-3-5-7-14/h3-9,12,17-19H,10-11H2,1-2H3/t17-/m1/s1
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| Chemical Name |
3-methyl-4-[(1R)-3-(methylamino)-1-phenylpropoxy]phenol
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| Synonyms |
4Hydroxyatomoxetine; 4 Hydroxyatomoxetine
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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) |
DMSO : ~125 mg/mL (~460.66 mM)
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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 | 3.6853 mL | 18.4264 mL | 36.8528 mL | |
| 5 mM | 0.7371 mL | 3.6853 mL | 7.3706 mL | |
| 10 mM | 0.3685 mL | 1.8426 mL | 3.6853 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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