| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
Human serotonin transporter (hSERT) with Ki = 40.2 ± 1.6 nM (radioligand binding) and IC50 = 47.3 ± 19.4 nM (5-HT uptake inhibition) [1]
Human norepinephrine transporter (hNET) with Ki (whole-cell) = 558.4 ± 121.6 nM, Ki (membrane) = 3385.1 ± 349.3 nM, and IC50 = 531.3 ± 113.0 nM (NE uptake inhibition) [1] Human dopamine transporter (hDAT): weak binding with 61.6% ± 1.7% inhibition at 100 μM, estimated Ki ≈ 25 ± 5 μM [1] |
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| ln Vitro |
The inhibition of CYP2D6 by desvenlafaxine succinate hydrate may lead to higher amounts of medications metabolized by this route. Additionally, desvenlafaxine succinate hydrate stimulates CYP3A4, which may have an impact on how medications that this enzyme metabolizes are metabolized [2].
Competitive radioligand binding assays showed that DVS potently inhibits [3H]citalopram binding at hSERT with Ki = 40.2 ± 1.6 nM. [1] In MDCK-hNET6 cells, DVS competitively inhibited [3H]nisoxetine binding (a known NE reuptake inhibitor) with Ki = 558.4 ± 121.6 nM; in hNET membranes, Ki = 3385.1 ± 349.3 nM. [1] Functional uptake assays: DVS inhibited [3H]5-HT uptake in JAR cells (hSERT) with IC50 = 47.3 ± 19.4 nM; inhibited [3H]NE uptake in MDCK-hNET6 cells with IC50 = 531.3 ± 113.0 nM. [1] Selectivity screening at 96 non-transporter targets (receptors, transporters, enzymes, channels) at 10 μM showed no significant activity except for 5-HT and NE transporters. [1] |
| ln Vivo |
Desvenlafaxine succinate hydrate (30 mg/kg, orally) dramatically raised extracellular NE levels using microdialysis, but had little effect on DA levels [1].
Oral administration of DVS (30 mg/kg) rapidly penetrated male rat brain and hypothalamus; Cmax in hypothalamus (963 ng/g) and total brain (771 ng/g) reached at 30 min post-dose. [1] Microdialysis in rat hypothalamus: DVS (30 mg/kg p.o.) alone did not significantly alter extracellular 5-HT levels (F(2,19)=0.74, P=0.4898), but when combined with WAY-100635 (5-HT1A antagonist, 0.3 mg/kg s.c.), 5-HT increased by 78% compared to baseline (F(1,9)=36.09, P=0.0001). [1] DVS (30 mg/kg p.o.) significantly increased extracellular NE levels: 118% above baseline (P=0.0034) compared to vehicle; 10 mg/kg gave 96% above baseline (P=0.0221). Combination with WAY-100635 did not further elevate NE. [1] DVS did not alter dopamine levels in hypothalamus either alone or with WAY-100635 (F(2,23)=0.18, P=0.8343). [1] |
| Enzyme Assay |
hSERT membrane radioligand binding assay: Membranes from HEK293 cells expressing hSERT were incubated with 1 nM [3H]citalopram, test compound (DVS) or buffer, and 0.5 mg/well wheat germ agglutinin SPA beads. Non-specific binding defined by 10 μM fluoxetine. After 1 h incubation at room temperature, plates were counted on a scintillation counter. Ki calculated using Cheng-Prusoff equation. [1]
hNET whole-cell radioligand binding assay: MDCK-hNET6 cells plated in 96-well plates were incubated with 3 nM [3H]nisoxetine and various concentrations of DVS (10–30,000 nM) in assay buffer (25 mM HEPES, 120 mM NaCl, 5 mM KCl, 2.5 mM CaCl2, 1.2 mM MgSO4, 2 mg/ml glucose, pH 7.4, with 0.2 mg/ml ascorbic acid and 1 μM pargyline) for 1.5 h at 37°C. Non-specific binding defined by 1 μM desipramine. After washing, bound radioactivity measured by scintillation counting. [1] hNET membrane radioligand binding assay: Membranes containing hNET were incubated with 3 nM [3H]nisoxetine and DVS (10–30,000 nM) in binding buffer (50 mM Tris-HCl, 300 mM NaCl, 5 mM KCl, pH 7.4) for 1 h at room temperature. Reaction terminated by vacuum filtration through PEI-soaked glass fiber filters, washed seven times, and counted. [1] hDAT membrane radioligand binding assay: Membranes from CHO cells expressing hDAT were incubated with 32 nM [3H]WIN-35,428 and DVS (100–100,000 nM) in binding buffer (50 mM Tris-HCl, 100 mM NaCl, pH 7.4) for 2 h at 4°C. Non-specific binding defined by 10 μM mazindol. Terminated by vacuum filtration through PEI-soaked filters, washed nine times, and counted. [1] 5-HT uptake assay: JAR cells (human placental choriocarcinoma) were stimulated with 40 nM staurosporine, then incubated with DVS (1–1000 nM) for 10 min at 37°C, followed by 15 nM [3H]5-HT for 9 min. Non-specific uptake defined by 1 μM paroxetine. Reaction terminated by decanting, cells washed, lysed with 0.25 N NaOH, and counted. [1] NE uptake assay: MDCK-hNET6 cells were incubated with DVS (1–10,000 nM) for 10 min at 37°C, then with 120 nM [3H]NE for 10 min. Non-specific uptake defined by 1 μM desipramine. Terminated by decanting, washed, lysed, and counted. [1] |
| Cell Assay |
HEK293 cells stably expressing hSERT were cultured in DMEM with 10% dialyzed FBS and 500 μg/ml G418. Cells were grown to 80-90% confluence in T175 flasks. For binding assays, cells were plated in 96-well plates. [1]
MDCK-Net6 cells stably expressing hNET were cultured in DMEM with 10% FBS and 500 μg/ml G418. Cells were plated at 300,000 cells/T75 flask and split twice weekly. For whole-cell binding and uptake assays, cells were plated at 3000-5000 cells/well in 96-well plates 24 h before assay. [1] JAR cell line (human placental choriocarcinoma) expressing hSERT was cultured in RPMI 1640 with 10% FBS, 1% sodium pyruvate, and 0.25% glucose. For 5-HT uptake assay, cells were plated at 15,000 cells/well in 96-well plates, then stimulated with 40 nM staurosporine to increase transporter expression. [1] |
| Animal Protocol |
Animal/Disease Models: Male rat [1].
Doses: 30 mg/kg. Mode of Route of Administration: Orally. Experimental Results: Using microdialysis, extracellular NE levels in the hypothalamus of male rats Dramatically increased compared with baseline, but had no effect on DA levels. Brain penetration study: Male Sprague-Dawley rats (2 months old) were orally dosed with DVS at 30 mg/kg in 0.25% Tween 80 and 0.5% methylcellulose (0.5 ml volume). Food was restricted from 4 h pre-dose to 20 min post-dose. At various time points (0.5, 1, 2, 4, 8, and 24 h), rats were anesthetized with 2% isoflurane/oxygen, blood collected by cardiac puncture, and then perfused with 40 ml cold phosphate-buffered saline. Brain and hypothalamus were dissected and homogenized for DVS concentration analysis by HPLC-MS. Three rats per time point. [1] Microdialysis study: Adult male Sprague-Dawley rats (280-330 g) were anesthetized with halothane and implanted with a microdialysis guide cannula directed to the preoptic area of hypothalamus (coordinates: -0.40 mm anterior to bregma, -1.0 mm from midline, -6.90 mm from dura). After 20-23 h recovery, a microdialysis probe (2 mm membrane) was inserted and perfused with artificial cerebrospinal fluid (125 mM NaCl, 3 mM KCl, 0.75 mM MgSO4, 1.2 mM CaCl2, pH 7.4) at 1 μl/min. After 3 h stabilization, five baseline samples (20 μl each) were collected. Then animals received WAY-100635 (0.3 mg/kg s.c.) or vehicle, followed 20 min later by DVS (30 mg/kg p.o.) or vehicle. Dialysate samples were collected every 20 min for at least 3 h and analyzed for NE, 5-HT, and DA by HPLC with electrochemical detection. n=6-9 per treatment group. [1] |
| ADME/Pharmacokinetics |
After oral administration of DVS at 30 mg/kg to male rats: plasma Cmax = 940 ng/ml at 30 min; terminal half-life = 2.1 h; AUC0-∞ = 1864 h·ng/ml; undetectable at 24 h. [1]
Hypothalamus: Cmax = 963 ng/g at 30 min; half-life = 2.2 h; AUC0-∞ = 3485 h·ng/g; undetectable at 24 h. [1] Total brain: Cmax = 771 ng/g at 30 min; half-life = 2.1 h; AUC0-∞ = 2923 h·ng/g; undetectable at 24 h. [1] Brain-to-plasma ratio: maximum hypothalamus-to-plasma ratio = 2.6 at 8 h; maximum total brain-to-plasma ratio = 2.2 at 2 h. Hypothalamus AUC/plasma AUC = 1.8; brain AUC/plasma AUC = 1.6. [1] |
| Toxicity/Toxicokinetics |
At 10 μM, DVS showed no significant activity at 96 non-transporter targets (including receptors, ion channels, enzymes, and other transporters), indicating high selectivity and low potential for off-target adverse effects. [1]
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| References | |
| Additional Infomation |
Desvenlafaxine succinate is the succinate form of desvenlafaxine, a synthetic phenylethylamine bicyclic derivative with antidepressant activity. Due to its high affinity for presynaptic serotonin and norepinephrine transporters, desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. By blocking these two transporters, the drug prolongs the activity of these two neurotransmitters, thereby alleviating depressive states. It is a derivative of cyclohexanol and phenol, and a metabolite of venlafaxine, acting as a serotonin and norepinephrine reuptake inhibitor (SNRI) and used as an antidepressant. See also: Desvenlafaxine (containing the active ingredient).
Drug Indications Treatment of major depressive disorder DVS is the succinate salt monohydrate of desvenlafaxine, the major active metabolite of venlafaxine. It is a new serotonin and norepinephrine reuptake inhibitor (SNRI). [1] Mechanism: DVS binds to presynaptic 5-HT and NE transporters, inhibiting reuptake and increasing extracellular concentrations of these neurotransmitters. It has weak affinity for the dopamine transporter. [1] Potential therapeutic utilities based on preclinical findings: major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, diabetic peripheral neuropathic pain, fibromyalgia, menopausal hot flashes, stress urinary incontinence, and other CNS- and peripheral-related disorders associated with disrupted 5-HT and NE levels. [1] The compound demonstrates good brain-to-plasma ratios and rapidly penetrates the CNS. Chronic treatment combined with 5-HT1A antagonism (e.g., WAY-100635) is predicted to produce sustained elevations of 5-HT. [1] |
| Molecular Formula |
C20H33NO7
|
|---|---|
| Molecular Weight |
399.2257
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| Exact Mass |
399.225
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| CAS # |
386750-22-7
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| Related CAS # |
Desvenlafaxine;93413-62-8;Desvenlafaxine succinate;448904-47-0;Desvenlafaxine fumarate;93414-04-1;Desvenlafaxine hydrochloride;300827-87-6
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| PubChem CID |
6918664
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| Appearance |
White to off-white solid powder
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| Boiling Point |
403.8ºC at 760 mmHg
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| Flash Point |
193.2ºC
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| LogP |
2.668
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
28
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| Complexity |
359
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| Defined Atom Stereocenter Count |
0
|
| InChi Key |
PWPDEXVGKDEKTE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H25NO2.C4H6O4.H2O/c1-17(2)12-15(13-6-8-14(18)9-7-13)16(19)10-4-3-5-11-16;5-3(6)1-2-4(7)8;/h6-9,15,18-19H,3-5,10-12H2,1-2H3;1-2H2,(H,5,6)(H,7,8);1H2
|
| Chemical Name |
4-(2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl)phenol succinate hydrate
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| Synonyms |
Desvenlafaxine Succinate hydrate；DVS 233；DVS233；DVS-233 WY-45233；WY 45233；WY45233；Pristiq
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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 : ≥ 33 mg/mL (~82.61 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume 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: ≥ 2.08 mg/mL (5.21 mM) (saturation unknown) 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. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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: ≥ 2.08 mg/mL (5.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5048 mL | 12.5241 mL | 25.0482 mL | |
| 5 mM | 0.5010 mL | 2.5048 mL | 5.0096 mL | |
| 10 mM | 0.2505 mL | 1.2524 mL | 2.5048 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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