| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Ampreloxetine TFA targets the norepinephrine (NE) and serotonin (5-HT) transporters, which are responsible for the reuptake of these neurotransmitters from the synaptic cleft. By inhibiting these transporters, Ampreloxetine TFA increases the extracellular concentrations of norepinephrine and serotonin, enhancing noradrenergic and serotonergic neurotransmission. Norepinephrine plays a critical role in blood pressure regulation, and its enhancement is the basis for the compound's potential use in neurogenic orthostatic hypotension.
|
|---|---|
| ln Vitro |
Ampreloxetine TFA shows potent in vitro activity as an inhibitor of norepinephrine (NE) and serotonin (5-HT) reuptake. The compound effectively blocks the reuptake of these neurotransmitters, leading to increased extracellular levels. The specific IC50 values for NE and 5-HT transporter inhibition have not been detailed in the available literature. As a reuptake inhibitor, Ampreloxetine TFA is expected to enhance noradrenergic and serotonergic neurotransmission.
|
| ln Vivo |
The EC50 values of ampreloxetine (0.3, 1, 5, 10, 30, 60 mg/kg; po; single dose) TFA in rat plasma were 11.7 ng/mL and 50.8 ng/mL, respectively[1].
In vivo activity of Ampreloxetine TFA has been suggested for the research of neurogenic orthostatic hypotension. As an orally active compound, Ampreloxetine TFA is suitable for convenient administration via oral gavage. The compound's ability to increase norepinephrine levels in vivo supports its potential for treating conditions associated with impaired noradrenergic function. |
| Enzyme Assay |
Non-cell-based binding assays for Ampreloxetine TFA typically involve measuring the affinity of the compound for the norepinephrine and serotonin transporters using radioligand binding assays. A standard protocol includes: preparing membrane preparations from cells expressing the NE or 5-HT transporters, incubating with a radiolabeled ligand (such as [3H]nisoxetine for NE transporter or [3H]paroxetine for 5-HT transporter), adding Ampreloxetine TFA at various concentrations, and measuring displacement of the radioligand to determine binding affinity (Ki).
|
| Cell Assay |
Cellular assays for Ampreloxetine TFA typically involve cells expressing the norepinephrine or serotonin transporters. A representative protocol includes: culturing cells (e.g., HEK293 cells transfected with NE or 5-HT transporters) in appropriate medium, loading cells with a fluorescent substrate for the transporter, treating with Ampreloxetine TFA at various concentrations (0.001–100 μM), and measuring inhibition of substrate uptake. The IC50 for reuptake inhibition is calculated from dose-response curves.
|
| Animal Protocol |
Animal/Disease Models: Male Sprague Dawley rats
Doses: 0.3, 1, 5, 10, 30, 60 mg/kg Route of Administration: P.o.; single dose Experimental Results: Showed good PK and PD parameter with Emax of 79%, 92% for SERT and NET, respectively; EC50 values of 50.8, 11.7 ng/mL for SERT, NET, respectively. In vivo animal studies with Ampreloxetine TFA are conducted in animal models of neurogenic orthostatic hypotension or other conditions involving noradrenergic dysfunction. A typical protocol involves administering the compound via oral gavage at doses determined from pharmacokinetic studies, measuring blood pressure and heart rate responses to postural changes, and assessing norepinephrine levels in plasma or brain tissue. The compound's effects on autonomic function and neurotransmitter levels are monitored. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Ampreloxetine TFA have been characterized for oral administration. The compound is orally active, supporting convenient administration. Ampreloxetine TFA has a molecular weight of 435.36 g/mol and a molecular formula of C20H19F6NO3. The compound is stored at -20°C, protected from light. Standard PK parameters including half-life, Cmax, and AUC can be determined from plasma concentration-time profiles following oral administration.
|
| Toxicity/Toxicokinetics |
As a research compound, Ampreloxetine TFA is not intended for human therapeutic use without further development, and comprehensive toxicological data are limited to preclinical studies. Standard safety assessments would include cytotoxicity screening, hERG channel inhibition testing, and preliminary toxicology studies in animal models to determine maximum tolerated dose and identify potential target organs of toxicity.
|
| References |
|
| Additional Infomation |
Ampreloxetine TFA (TD-9855 TFA, CAS 1227056-85-0) is a potent and orally active norepinephrine (NE) and serotonin (5-HT) reuptake inhibitor. Ampreloxetine TFA has the potential for the research of neurogenic orthostatic hypotension. The compound is available as a research reagent for neuroscience and cardiovascular research applications.
|
| Molecular Formula |
C20H19F6NO3
|
|---|---|
| Molecular Weight |
435.4
|
| Exact Mass |
435.126912
|
| CAS # |
1227056-85-0
|
| Related CAS # |
Ampreloxetine hydrochloride;1227056-87-2; 1227056-84-9; 1227056-85-0 (TFA)
|
| PubChem CID |
134280433
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
30
|
| Complexity |
436
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CNCCC1C2=CC=CC=C2COC3=C(C=C(C=C3F)F)F.C(=O)(C(F)(F)F)O
|
| InChi Key |
MDURTULDKWJPAB-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H18F3NO.C2HF3O2/c19-14-9-16(20)18(17(21)10-14)23-11-13-3-1-2-4-15(13)12-5-7-22-8-6-12;3-2(4,5)1(6)7/h1-4,9-10,12,22H,5-8,11H2;(H,6,7)
|
| Chemical Name |
2,2,2-trifluoroacetic acid;4-[2-[(2,4,6-trifluorophenoxy)methyl]phenyl]piperidine
|
| Synonyms |
Ampreloxetine (TFA); 1227056-85-0; Ampreloxetine TFA; SCHEMBL19895303; TD-9855 (TFA);
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO :~100 mg/mL (~229.69 mM; with sonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.74 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 25.0 mg/mL clear DMSO stock solution and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.74 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 25.0 mg/mL clear DMSO stock solution and add it to 900 μL of 20% SBE-β-CD saline solution and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (5.74 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2967 mL | 11.4837 mL | 22.9674 mL | |
| 5 mM | 0.4593 mL | 2.2967 mL | 4.5935 mL | |
| 10 mM | 0.2297 mL | 1.1484 mL | 2.2967 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
