| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
The primary target of (+/-)-Darifenacin is the M3 muscarinic acetylcholine receptor (mAChR), for which it exhibits high affinity and selectivity. Darifenacin binds to all five subtypes of muscarinic receptors but is targeted to the M3 subtype for which it is selective. It may also interact with p53-MDM2, contributing to its potential anticancer activity. As a competitive antagonist, it blocks receptor activation by competing with acetylcholine at the binding site.
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| ln Vitro |
In vitro studies have shown that (+/-)-Darifenacin effectively antagonizes M3 muscarinic receptors in guinea pig bladder tissue, with preclinical data indicating functional selectivity. The compound's ability to inhibit p53-MDM2 interaction suggests potential anticancer activity in vitro. As a racemate, it may exhibit slightly different potency compared to the pure enantiomer, though darifenacin itself is used clinically as the (S)-enantiomer. In vitro solubility studies show the compound is soluble in DMSO at 100 mg/mL (234.44 mM).
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| ln Vivo |
In vivo, (+/-)-Darifenacin (as Darifenacin) has been studied in preclinical animal models including rats and dogs, demonstrating efficacy in reducing bladder contractions and treating overactive bladder symptoms. The selective M3 receptor antagonism translates to therapeutic effects on urinary bladder function. The compound can be formulated for oral administration, with solubility achieved in formulations such as 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline or 10% DMSO + 90% corn oil, yielding clear solutions at ≥ 2.5 mg/mL (5.86 mM).
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| Enzyme Assay |
For receptor binding assays to assess M3 muscarinic receptor antagonism, use radioligand binding with [3H]-N-methylscopolamine in membrane preparations from cells expressing human M3 receptors. Incubate membranes (20-50 ug) with varying concentrations of (+/-)-Darifenacin (0.001-10 uM) and a fixed concentration of radioligand for 60 min at room temperature in binding buffer (50 mM Tris-HCl pH 7.4, 5 mM MgCl2). Terminate incubation by rapid filtration through GF/B filters, wash with ice-cold buffer, and measure radioactivity. Calculate IC₅0 from competition curves and determine Ki using the Cheng-Prusoff equation.
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| Cell Assay |
Culture CHO or HEK-293 cells stably expressing human M3 muscarinic receptors in DMEM with 10% FBS at 37degC with 5% CO2. For calcium mobilization assays, seed cells (2-4×10⁴ per well) in 96-well plates overnight. Load cells with calcium-sensitive dye (e.g., Fluo-4 AM) in HBSS with 20 mM HEPES for 60 min at 37degC. Wash and add varying concentrations of (+/-)-Darifenacin (0.1 nM to 10 uM) and incubate for 10-20 min, then stimulate with carbachol (EC₈0 concentration). Measure fluorescence changes using a microplate reader. Calculate IC₅0 for inhibition of calcium flux. For cell viability in cancer models, treat p53-expressing cancer cells with (+/-)-Darifenacin (1-100 uM) for 48-72 h and assess using MTT assay.
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| Animal Protocol |
For in vivo efficacy studies of Darifenacin or its racemate, use adult Sprague-Dawley rats (200-250 g) or CD-1 mice (20-25 g). For bladder contractility studies, anesthetize animals with urethane (1.2 g/kg i.p.) and perform cystometry via a bladder catheter. Administer (+/-)-Darifenacin intravenously (0.01-1 mg/kg) or orally (0.1-10 mg/kg) suspended in vehicle (e.g., 0.5% methylcellulose or 10% DMSO/90% corn oil). For overactive bladder models, induce bladder hyperactivity with intravesical acetic acid or intraperitoneal cyclophosphamide. Monitor bladder pressure, voiding frequency, and intercontraction intervals for 60-120 min post-dose. Collect blood at multiple time points for pharmacokinetic analysis.
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| ADME/Pharmacokinetics |
For (+/-)-Darifenacin, solubility studies show it is soluble in DMSO at 100 mg/mL (234.44 mM) and can be formulated for in vivo use in clear solutions at ≥ 2.5 mg/mL in vehicles including 10% DMSO/40% PEG300/5% Tween-80/45% saline, 10% DMSO/90% (20% SBE-beta-CD in saline), or 10% DMSO/90% corn oil. The compound should be stored as a powder at -20degC for up to 3 years and in solvent at -80degC for 6 months. Its pharmacokinetic profile as the active enantiomer darifenacin shows good oral bioavailability and systemic exposure.
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| Toxicity/Toxicokinetics |
The safety and tolerability of Darifenacin have been clinically established as an approved medication for overactive bladder. For the racemic mixture (+/-)-Darifenacin used in research, standard precautions apply. The compound should be handled with care: use personal protective equipment, avoid inhalation and skin contact. At typical research concentrations (e.g., ≤10 uM in cell culture or ≤10 mg/kg in animals), it is well-tolerated. No specific teratogenic or carcinogenic concerns have been reported for the research-grade racemic product. Always consult the safety data sheet before handling. This product is for research use only and not intended for human use.
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| References | |
| Additional Infomation |
See also: Dafinax (note moved to).
Darifenacin, the (S)-enantiomer, is an FDA-approved medication for the treatment of overactive bladder (OAB) with symptoms of urinary frequency, urgency, and urge incontinence. (+/-)-Darifenacin is the racemic form used primarily for research purposes. It has also been investigated for potential applications in Alzheimer's disease and Parkinson's disease due to modulation of cholinergic pathways. The compound's mechanism as an M3-selective antagonist reduces detrusor muscle contractions without significantly affecting salivary or gastrointestinal function, offering a favorable side effect profile compared to non-selective antimuscarinics. |
| Molecular Formula |
C28H30N2O2
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|---|---|
| Molecular Weight |
426.550007343292
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| Exact Mass |
426.23
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| CAS # |
133033-93-9
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| Related CAS # |
Darifenacin hydrobromide;133099-07-7;(±)-Darifenacin-d4;1189701-43-6;(±)-Darifenacin-d4 hydrobromide;2747914-16-3;Darifenacin;133099-04-4
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| PubChem CID |
72054
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| Appearance |
White to off-white solid powder
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| LogP |
4.6
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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 |
32
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| Complexity |
607
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C(C1C=CC=CC=1)(C1C=CC=CC=1)C1CN(CCC2C=CC3=C(CCO3)C=2)CC1)N
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| InChi Key |
HXGBXQDTNZMWGS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H30N2O2/c29-27(31)28(23-7-3-1-4-8-23,24-9-5-2-6-10-24)25-14-17-30(20-25)16-13-21-11-12-26-22(19-21)15-18-32-26/h1-12,19,25H,13-18,20H2,(H2,29,31)
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| Chemical Name |
2-[1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide
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| Synonyms |
(±)Darifenacin; (±) Darifenacin
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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 : ~100 mg/mL (~234.44 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.86 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 25.0 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: ≥ 2.5 mg/mL (5.86 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 25.0 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: ≥ 2.5 mg/mL (5.86 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 | 2.3444 mL | 11.7220 mL | 23.4439 mL | |
| 5 mM | 0.4689 mL | 2.3444 mL | 4.6888 mL | |
| 10 mM | 0.2344 mL | 1.1722 mL | 2.3444 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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