| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Noradrenaline Transporter (NET). 4-Hydroxyatomoxetine D3 acts via inhibition of the presynaptic norepinephrine transporter (NET) in the brain. By blocking norepinephrine reuptake into presynaptic terminals, it increases extracellular norepinephrine levels in the prefrontal cortex (PFC), enhancing noradrenergic transmission and improving attention, impulsivity, and hyperactivity in ADHD.
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| ln Vitro |
4-Hydroxyatomoxetine inhibits [3H]norepinephrine uptake into rat synaptosomes (IC50 approximately 5-10 nM), with potency similar to atomoxetine (IC50 = 5 nM). It is highly selective for NET over serotonin (5-HT) and dopamine (DAT) transporters. The deuterated form retains this NET inhibitory activity and serves as a stable labeled tracer.
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| ln Vivo |
In animal models, atomoxetine (0.3-3 mg/kg i.p.) increases extracellular norepinephrine and dopamine levels in the prefrontal cortex (by 200-300%) but not in the nucleus accumbens or striatum, as measured by microdialysis. This regional selectivity is thought to underlie its therapeutic efficacy in ADHD without abuse potential. The active metabolite 4-hydroxyatomoxetine contributes to the overall in vivo activity.
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| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from HEK-293 cells expressing human NET. Membranes (10-50 microg protein) are incubated with [3H]nisoxetine as the radioligand and varying concentrations of 4-hydroxyatomoxetine D3 in 50 mM Tris-HCl buffer (pH 7.4) containing 120 mM NaCl and 5 mM KCl for 60 minutes at 4degC. Nonspecific binding is determined with 10 microM desipramine. Bound radioactivity is separated by filtration through GF/B filters and measured by liquid scintillation counting. Ki values are calculated using the Cheng-Prusoff equation.
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| Cell Assay |
HEK-293 cells stably expressing human NET are seeded in 96-well plates (100,000 cells/well) in DMEM with 10% FBS. After 24 hours, cells are washed with Krebs-HEPES buffer (pH 7.4) containing 10 microM pargyline and 0.5 mM ascorbic acid. Cells are pre-incubated with varying concentrations of 4-hydroxyatomoxetine D3 for 10 minutes, then [3H]norepinephrine (100 nM) is added for 10 minutes at 37degC. Uptake is terminated by washing cells three times with ice-cold buffer, and cell lysates are collected for scintillation counting. IC50 values are calculated from inhibition curves.
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| Animal Protocol |
Male Sprague-Dawley rats (250-300 g) undergo stereotaxic surgery for implantation of a microdialysis probe into the prefrontal cortex (coordinates: AP +3.2 mm, ML +/-0.8 mm, DV -4.5 mm from bregma). After 24-48 hours recovery, artificial cerebrospinal fluid (aCSF) is perfused at 1.5 microL/min. Dialysate samples are collected every 20 minutes. After baseline stabilization (3-4 samples), 4-hydroxyatomoxetine (1-10 mg/kg i.p.) or vehicle is administered. Norepinephrine and dopamine levels in dialysate are quantified by HPLC-ECD. The percent increase over baseline is calculated.
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| ADME/Pharmacokinetics |
4-Hydroxyatomoxetine D3 is intended as an internal standard for LC-MS/MS quantification of atomoxetine and its metabolites. 4-Hydroxyatomoxetine is formed by CYP2D6-mediated aromatic hydroxylation of atomoxetine. In humans, atomoxetine has an oral bioavailability of ~63-94%, a half-life of 4-5 hours in extensive metabolizers (EMs) and ~21 hours in poor metabolizers (PMs), and is 98% protein bound.
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| Toxicity/Toxicokinetics |
Atomoxetine is generally well tolerated but carries a boxed warning for suicidal ideation in children and adolescents. Common adverse effects include gastrointestinal distress (nausea, vomiting, decreased appetite), dry mouth, insomnia, fatigue, and dizziness. Cardiovascular effects (mild increases in heart rate and blood pressure) may occur. Hepatotoxicity is rare but can be severe.
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| References | |
| Additional Infomation |
Atomoxetine (Strattera®) was FDA-approved in 2002 for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. 4-Hydroxyatomoxetine D3 is a research internal standard used in pharmaceutical analysis, drug metabolism studies, therapeutic drug monitoring, and forensic toxicology for the precise quantification of atomoxetine and its active metabolite.
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| Molecular Formula |
C17H18D3NO2
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|---|---|
| Molecular Weight |
274.3723
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| Exact Mass |
274.176
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| CAS # |
1217686-14-0
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| Related CAS # |
4-Hydroxyatomoxetine;435293-66-6
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| PubChem CID |
45039401
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| Appearance |
Light yellow to yellow solid powder
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| Melting Point |
121-123°C
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| LogP |
3.4
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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 |
[2H]C([2H])([2H])NCC[C@H](C1=CC=CC=C1)OC2=C(C=C(C=C2)O)C
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| InChi Key |
PPXQPRLGNSJNJM-NVNSKBCASA-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/i2D3
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| Chemical Name |
3-methyl-4-[(1R)-1-phenyl-3-(trideuteriomethylamino)propoxy]phenol
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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 | 3.6447 mL | 18.2236 mL | 36.4471 mL | |
| 5 mM | 0.7289 mL | 3.6447 mL | 7.2894 mL | |
| 10 mM | 0.3645 mL | 1.8224 mL | 3.6447 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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