| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Nisoxetine's primary target is the noradrenaline transporter (NET). It acts as a potent and selective inhibitor of NET, with a Kd of 0.76 nM. It exhibits approximately 1000-fold greater potency in blocking norepinephrine uptake compared to serotonin and 400-fold compared to dopamine. By inhibiting NET, it prevents the reuptake of norepinephrine, increasing its concentration in the synaptic cleft and enhancing noradrenergic signaling.
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| ln Vitro |
At a Ki of 1.4±0.1 nM, nisoxetine prevents [3H]nisoxetine from attaching to the frontal cortex membrane[2]. With a Ki of 2.1, nisoxetine decreases the amount of [3H]norphine in frontal lobe synaptosomes. When applied to membrane potentials of -70 and -100 mV, nisoxetine inhibits Na+ currents with IC50s of 1.6 and 28.6 μM, respectively. ±0.3 nM[3].
In vitro, Nisoxetine is characterized by its high affinity and selectivity for the norepinephrine transporter (NET). It is a potent inhibitor of [³H]-norepinephrine uptake in synaptosomes or cell lines expressing NET. Its selectivity for NET over the serotonin transporter (SERT) and dopamine transporter (DAT) makes it a valuable tool for studying noradrenergic function. It also acts as a local anesthetic by blocking voltage-gated sodium channels. |
| ln Vivo |
Nisoxetine (2.2 µM; single intrathecal injection) blocks motor function and proprioception 100%, 100%, and 100% of the time, with half-lives of roughly 61, 96, and 236 minutes, respectively [3]. In rats, the ingestion of standard food during the refeeding response is inhibited by nisoxetine (3, 10, 30 mg/kg, ip) [4].
In vivo, Nisoxetine has been used in animal studies to investigate the role of norepinephrine in various physiological processes. For example, it has been used to study the effects of norepinephrine reuptake inhibition on feeding behavior, particularly in the context of diet-induced alterations in feeding suppression. Its effects are attributed to the increased availability of norepinephrine in the synaptic cleft. |
| Enzyme Assay |
The in vitro affinity of Nisoxetine for the norepinephrine transporter (NET) is determined using radioligand binding or uptake inhibition assays. In a typical cell-free or cell-based protocol, membranes from cells expressing NET are incubated with a radiolabeled ligand (e.g., [³H]-nisoxetine or [³H]-desipramine) and varying concentrations of unlabeled Nisoxetine. The amount of bound radioligand is measured, and the Ki or Kd is calculated.
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| Cell Assay |
Cellular assays for Nisoxetine involve studying its effect on norepinephrine uptake. In a typical protocol, cells expressing the norepinephrine transporter (NET) are incubated with [³H]-norepinephrine in the presence or absence of Nisoxetine. After a set period, the cells are washed, and the amount of accumulated radioactivity is measured. The IC50 for inhibition of norepinephrine uptake is then calculated.
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| Animal Protocol |
Animal/Disease Models: SD (SD (Sprague-Dawley)) rat (290-340 g) [3]
Doses: 0.6, 1.2, 1.8, 2.2 µM Route of Administration: Single intrathecal injection Experimental Results: Blocked motor function, proprioception, and nociception respectively. The in vivo activity of Nisoxetine has been studied in animal models, particularly in the context of feeding behavior. In a typical protocol, rats are administered Nisoxetine via intraperitoneal or oral administration. Food intake is then measured over a set period. The compound's ability to suppress food intake is assessed, and the effects of various conditions (e.g., high-fat diet) on its efficacy are evaluated. |
| ADME/Pharmacokinetics |
Nisoxetine has a molecular weight of 289.37 and a molecular formula of C₁₇H₁₉NO₂·HCl. It is typically supplied as a hydrochloride salt for enhanced solubility. It is a research standard SNRI. As a research chemical, detailed pharmacokinetic data are not typically reported for clinical use, as it is not an approved drug. However, its properties are well-characterized for in vitro and in vivo studies.
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| Toxicity/Toxicokinetics |
The toxicity of Nisoxetine is related to its mechanism of action. As a norepinephrine reuptake inhibitor, it can cause cardiovascular effects, such as increased heart rate and blood pressure, due to enhanced noradrenergic signaling. As a local anesthetic, it can also affect nerve conduction. Its safety profile was evaluated during its development as an antidepressant, but it was not advanced to clinical use.
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| References |
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| Additional Infomation |
Nisoxetine is a secondary amine compound with the structure N-methyl-3-phenylprop-1-amine, substituted at the 3-position with a 2-methoxyphenoxy group. It has antidepressant and adrenergic reuptake inhibitor (SNRI) effects. It is an aromatic ether and also a secondary amine compound. Nisoxetine is a selective norepinephrine reuptake inhibitor (SNRI) developed in the 1970s. Initially, it was investigated for its antidepressant effects, but currently, it has no clinical applications other than as an investigational SNRI. It has been used in studies on obesity and energy balance and has some local analgesic effects.
Nisoxetine is a selective norepinephrine reuptake inhibitor (SNRI) that was developed as a potential antidepressant but is now used primarily as a research standard. It is a potent and selective inhibitor of the norepinephrine transporter (NET), with a Kd of 0.76 nM. It is also a local anesthetic that blocks voltage-gated sodium channels. It remains a valuable tool for studying noradrenergic signaling in preclinical research. |
| Molecular Formula |
C17H21NO2
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|---|---|
| Molecular Weight |
271.35414
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| Exact Mass |
271.157
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| Elemental Analysis |
C, 75.25; H, 7.80; N, 5.16; O, 11.79
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| CAS # |
53179-07-0
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| Related CAS # |
Nisoxetine hydrochloride;57754-86-6
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| PubChem CID |
4500
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| Appearance |
Colorless to light yellow solid powder
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| Density |
1.054g/cm3
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| Boiling Point |
404.8ºC at 760mmHg
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| Flash Point |
170.6ºC
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| Index of Refraction |
1.547
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| LogP |
3.815
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
20
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| Complexity |
253
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CNCCC(C1=CC=CC=C1)OC2=CC=CC=C2OC
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| InChi Key |
ITJNARMNRKSWTA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H21NO2/c1-18-13-12-15(14-8-4-3-5-9-14)20-17-11-7-6-10-16(17)19-2/h3-11,15,18H,12-13H2,1-2H3
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| Chemical Name |
3-(2-methoxyphenoxy)-N-methyl-3-phenylpropan-1-amine
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| Synonyms |
Nisoxetine
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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 : ~250 mg/mL (~921.32 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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