| Size | Price | |
|---|---|---|
| 250mg | ||
| 500mg | ||
| 1g | ||
| 2g |
[1] bioRxiv preprint
| Targets |
Serotonin (IC50 = 723 nM); dopamine (IC50 = 491 nM); norepinephrine (IC50 = 763 nM)
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|---|---|
| ln Vitro |
Triple reuptake inhibitors (TRIs) are currently being developed as a new class of promising antidepressants that block serotonin (5-HT), dopamine (DA) and norepinephrine (NE) transporters, thereby increasing extracellular monoamine concentrations. The purpose of this study was to investigate the effects of LPM570065, a novel TRI and a desvenlafaxine prodrug, on extracellular 5-HT, DA and NE levels in the rat striatum after acute and chronic administration relative to desvenlafaxine, using High Performance Liquid Chromatography (HPLC) and microdialysis[1].
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| ln Vivo |
Ansofaxine enters the rat striatum quickly, transforms into desvenlafaxine, and shows a greater overall exposure when compared to when desvenlafaxine is administered. The administration of oral suspension of ansofaxine, both acutely and chronically, is associated with higher levels of 5-HT, dopamine, and norepinephrine than is the case with desvenlafaxine administration. Acute intravenous ansofaxine solution administration does not result in the unwanted 90% reduction in extracellular 5-HT levels, in contrast to desvenlafaxine. When combined with WAY-100635, acute ansofaxine administration results in a capped increase in extracellular 5-HT levels. More so than desvenlafaxine administration in comparison, ansofaxine administration, both acute and chronic, shortens the period of immobility[1].
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| Animal Protocol |
Rats: This study uses oral solutions, oral suspensions, and intravenous solutions of ansofaxine and desvenlafaxine to investigate the effects of acute administration on extracellular 5-HT, DA, and NE levels. When 5-HT1A receptors are blocked by pretreatment with WAY-100635, an equal number of animals are used to investigate the acute effects of ansofaxine and desvenlafaxine on extracellular 5-HT levels. Pets are split into three groups at random for the 14-day chronic administration. Every day for 14 days, oral suspensions of desvenlafaxine, ansofaxine, and vehicle are given. The impact of ansofaxine and desvenlafaxine on extracellular 5-HT, DA, and NE levels is investigated on the fourteenth day of chronic administration[1].
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| References |
[1]. The effects of LPM570065, a novel triple reuptake inhibitor, on extracellular serotonin, dopamineand norepinephrine levels in rats. PLoS One. 2014 Mar 10;9(3):e91775.
:[2]. Efficacy, Safety, and Tolerability of Ansofaxine (LY03005) Extended-Release Tablet for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Clinical Trial. Int J Neuropsychopharmacol. 2021 Nov 8:pyab074
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| Additional Infomation |
Background: Ansofaxine (LY03005) extended-release tablet is a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. This study assessed the efficacy, safety, and appropriate dosage of ansofaxine for the treatment of major depressive disorder (MDD).[2]
Methods: A multicenter, randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial was conducted in China. Eligible patients with MDD (18-65 years) were randomly assigned to receive fixed-dose ansofaxine extended-release tablets (40, 80, 120, or 160 mg/d) or placebo for 6 weeks. The primary outcome measure was a change in the total score on the 17-item Hamilton Depression Rating Scale from baseline to week 6.[2] Results: A total of 260 patients were recruited from October 2015 to September 2017, and 255 patients received the study drug as follows: 40 mg (n = 52), 80 mg (n = 52), 120 mg (n = 51), and 160 mg (n = 51) ansofaxine and placebo (n = 49). Significant differences were found in mean changes in 17-item Hamilton Depression Rating Scale total scores at week 6 in the 4 ansofaxine groups vs placebo (-12.46; χ2 = -9.71, P = .0447). All doses of ansofaxine were generally well-tolerated. Treatment-related adverse events occurred in 141 patients (303 cases), yielding incidence rates of 51.92%, 65.38%, 56.86%, and 62.75% in the 40-, 80-, 120-, and 160-mg ansofaxine groups and 38.78% in the placebo group.[2] Conclusion: Active doses (40, 80, 120, and 160 mg/d) of ansofaxine in a controlled setting were safe, tolerated, and effective in improving depression symptoms in MDD patients. |
| Molecular Formula |
C24H31NO3
|
|---|---|
| Molecular Weight |
381.52
|
| Exact Mass |
381.230408
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| Elemental Analysis |
C, 75.56; H, 8.19; N, 3.67; O, 12.58
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| CAS # |
916918-80-4
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| Related CAS # |
Ansofaxine hydrochloride;916918-84-8
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| PubChem CID |
15983287
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
526.4±45.0 °C at 760 mmHg
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| Flash Point |
272.1±28.7 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.581
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| LogP |
4.83
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| tPSA |
49.8Ų
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| SMILES |
CN(C)CC(c1ccc(OC(=O)c2ccc(C)cc2)cc1)C3(O)CCCCC3
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| InChi Key |
QKYBZJLEMOZFFU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H31NO3/c1-18-7-9-20(10-8-18)23(26)28-21-13-11-19(12-14-21)22(17-25(2)3)24(27)15-5-4-6-16-24/h7-14,22,27H,4-6,15-17H2,1-3H3
|
| Chemical Name |
4-(2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl)phenyl 4-methylbenzoate
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| Synonyms |
Ansofaxine; LPM-570065; LY03005 toludesvenlafaxinum; Toludesvenlafaxine; LPM570065; ODVP2; Odesmethylvenlafaxine 4-methylbenzoate ester.
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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 | 2.6211 mL | 13.1055 mL | 26.2109 mL | |
| 5 mM | 0.5242 mL | 2.6211 mL | 5.2422 mL | |
| 10 mM | 0.2621 mL | 1.3105 mL | 2.6211 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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