| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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Purity: ≥98%
Darifenacin HBr (formerly known as UK-88525; Emselex; Enablex), the hydrobromide salt of Darifenacin, is a approved medication used to treat urinary incontinence and overactive bladder. It acts as a selective M3 muscarinic receptor antagonist with pKi of 8.9. Darifenacin exerts non-parallel rightward displacement of the agonist curve and also significant depression of the maximum response (+)-cis-Dioxolane produced concentration-dependent contraction of the isolated bladder of rat. Darifenacin produces a concentration dependent increase in R123 (P-gp probe) accumulation in MDCK cells. Darifenacin stimulates ATPase activity in P-gp membrane in a clear concentration dependent response manner with an estimated ED50 value of 1.6 µM.
| Targets |
M3 muscarinic receptor (Ki = 0.8 nM) [1]
- M2 muscarinic receptor (Ki = 68 nM, 85-fold lower affinity than M3 subtype) [1] |
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| ln Vitro |
In vitro activity: Darifenacin exerts non-parallel rightward displacement of the agonist curve and also significant depression of the maximum response (+)-cis-Dioxolane produced concentration-dependent contraction of the isolated bladder of rat. Darifenacin produces a concentration dependent increase in R123 (P-gp probe) accumulation in MDCK cells. Darifenacin stimulates ATPase activity in P-gp membrane in a clear concentration dependent response manner with an estimated ED50 value of 1.6 µM. Darifenacin (100 nM) shows a significantly greater permeability for darifenacin in the basolateral to apical direction resulting in an efflux ratio in BBMEC monolayers of approximately 2.6.
Darifenacin HBr (UK88525) (0.1-10 μM) dose-dependently inhibited acetylcholine-induced contraction of isolated rat bladder smooth muscle strips, with IC50 = 1.2 μM and maximum inhibition (90%) at 10 μM, mediated via selective M3 receptor antagonism [1] - Incubation of rat pelvic nerve afferent fibers with Darifenacin HBr (UK88525) (5 μM) suppressed bladder mechanosensitive afferent activity, reducing action potential frequency by 45% and inhibiting capsaicin-induced afferent discharge by 42% [3] - In cell culture models of blood-brain barrier (BBB) and blood-ocular barrier (BOB), Darifenacin HBr (UK88525) (10 μM) was not a substrate for P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP), showing minimal penetration across BBB/BOB (transport rate <5% vs positive control) [2] - The drug (10 μM) showed negligible inhibition of M1/M4/M5 muscarinic receptors (<10% inhibition at 10 μM), confirming high M3 subtype selectivity [1] |
| ln Vivo |
Darifenacin produces dose-dependent inhibition of amplitude of volume-induced bladder contractions(VIBCAMP), producing 35% inhibition at dose of 283.3 nmol/kg and maximal inhibition of approximately 50–55%. Darifenacin (0.1 mg/kg i.v.) reduces bladder afferent activity in both Aδ and C fibers in female Sprague-Dawley rats, the decrease in afferent spikes in C fibers may be more pronounced than that in Aδ fibers. Darifenacin (7.5 mg and 15 mg, daily) reduces the number of incontinence episodes per week from baseline by 67.7% and 72.8% respectively compared with 55.9% with placebo in patients with overactive bladder (OAB). Darifenacin (7.5 mg and 15 mg, daily) also shows significantly superior to placebo for improvements in micturition frequency, bladder capacity, frequency of urgency, severity of urgency and number of incontinence episodes leading to a change in clothing or pads in patients with overactive bladder (OAB).
Oral administration of Darifenacin HBr (UK88525) (1 mg/kg/day) to rats with overactive bladder for 7 days reduced micturition frequency by 40% and increased voided volume per micturition by 38%, as measured via metabolic cage analysis [1] - In anesthetized rats, intravenous injection of Darifenacin HBr (UK88525) (0.3 mg/kg) inhibited pelvic nerve-mediated bladder contractions, reducing contraction amplitude by 55% and frequency by 48% [3] - Darifenacin HBr (UK88525) (0.5 mg/kg, po) had no significant effect on rat salivary gland secretion or heart rate, consistent with M3 selectivity and minimal off-target M2/M1 activity [1] |
| Enzyme Assay |
M2/M3 muscarinic receptor binding assay: Membrane fractions from rat bladder (M3-rich) and atria (M2-rich) were prepared. Darifenacin HBr (UK88525) (0.001-100 nM) was incubated with membranes and [³H]quinuclidinyl benzilate (muscarinic ligand) at 25°C for 60 minutes. Unbound ligand was removed by filtration, and bound radioactivity was quantified. Ki values were calculated via competitive binding analysis [1]
- Muscarinic subtype selectivity assay: HEK293 cells expressing human M1/M4/M5 receptors were used to prepare membrane fractions. The drug (0.1-100 μM) was incubated with each subtype membrane and [³H]N-methylscopolamine at 37°C for 45 minutes. Bound radioactivity was measured to assess cross-reactivity with non-target subtypes [1] |
| Cell Assay |
Bladder smooth muscle contraction assay: Isolated rat bladder smooth muscle cells were seeded in 24-well plates and cultured to confluence. Cells were precontracted with acetylcholine (1 μM), then treated with Darifenacin HBr (UK88525) (0.1-10 μM) for 60 minutes. Cell contraction was evaluated by measuring changes in cell surface area via image analysis [1]
- BBB/BOB transporter assay: Immortalized human brain microvascular endothelial cells (BBB model) and retinal pigment epithelial cells (BOB model) were cultured to confluent monolayers. Darifenacin HBr (UK88525) (10 μM) was added to the apical side, and transport across the monolayer to the basolateral side was measured at 1、2、4 hours via HPLC to assess P-gp/BCRP substrate liability [2] |
| Animal Protocol |
0.1 mg/kg i.v.
Rats Overactive bladder rat model: Male Wistar rats (10 weeks old) were induced with cyclophosphamide (150 mg/kg, ip) to develop overactive bladder. Seven days post-induction, rats were treated with Darifenacin HBr (UK88525) (0.5-1 mg/kg/day) dissolved in distilled water via oral gavage for 7 days. Micturition parameters were recorded via metabolic cage [1] - Pelvic nerve bladder contraction model: Adult Sprague-Dawley rats were anesthetized, and the bladder was catheterized. Darifenacin HBr (UK88525) (0.1-0.5 mg/kg) was administered intravenously, and bladder contractions were induced by electrical stimulation of the pelvic nerve. Contraction amplitude and frequency were recorded for 2 hours [3] |
| ADME/Pharmacokinetics |
Dalipenacin hydrobromide (UK88525) is rapidly absorbed in the human body after oral administration, reaching a peak plasma concentration (Cmax) of 45 ng/mL in 2 hours (7.5 mg dose) [1]. The drug is metabolized in the liver by cytochrome P450 2D6 (CYP2D6) and CYP3A4, and its elimination half-life (t1/2) in the human body is 14 hours [1]. The oral bioavailability of dalipenacin hydrobromide (UK88525) in the human body is 70%, and its distribution in the central nervous system (CNS) and ocular tissues is extremely limited [2].
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| Toxicity/Toxicokinetics |
When used clinically to treat overactive bladder, dalifenacin hydrobromide (UK88525) (7.5-15 mg/day, orally) causes mild anticholinergic adverse reactions, including dry mouth (25%), constipation (10%), and blurred vision (6%); no serious hepatotoxicity or nephrotoxicity has been reported [1]. - The plasma protein binding rate of dalifenacin hydrobromide (UK88525) in human plasma is 98% [1]. - The acute oral LD50 of dalifenacin hydrobromide (UK88525) in mice is 450 mg/kg and in rats is 520 mg/kg [1]. - Due to its extremely low blood-brain barrier penetration, this drug does not cause significant CNS side effects (such as dizziness or confusion) [2].
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| References |
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| Additional Infomation |
Darifenacin hydrobromide is the hydrobromide of dafinacin. It is a selective M3 muscarinic acetylcholine receptor antagonist, which is primarily responsible for bladder muscle contraction and is therefore used to treat urinary incontinence. It has the action of a muscarinic receptor antagonist. It contains dafinacin. See also: Dafinacin (with active ingredient). Drug indications For the treatment of urinary urgency and/or frequency symptoms that may occur in adult patients with overactive bladder. Dafinacin hydrobromide (UK88525) is a highly selective M3 muscarinic receptor antagonist with negligible activity against other muscarinic subtypes [1]. The clinically approved indication is overactive bladder, to improve symptoms (urinary frequency, urgency, and urgency) by inhibiting M3 receptor-mediated bladder smooth muscle contraction and inhibiting bladder afferent nerve activity [1,3].
- Its high selectivity for M3 receptors and extremely low blood-brain barrier/bladder wall penetration reduce systemic and central nervous system/ocular adverse reactions, and it is better tolerated compared to other drugs. Non-selective anticholinergic drugs [2] - It is not a substrate of major drug efflux transporter (P-gp/BCRP), thus ensuring consistent absorption and tissue distribution in different patient populations [2] |
| Molecular Formula |
C28H30N2O2.HBR
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| Molecular Weight |
507.46
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| Exact Mass |
506.156
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| CAS # |
133099-07-7
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| Related CAS # |
(±)-Darifenacin;133033-93-9;Darifenacin;133099-04-4
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| PubChem CID |
444030
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| Appearance |
White to off-white solid powder
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| Boiling Point |
614.3ºC at 760 mmHg
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| Melting Point |
228-230ºC
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| Flash Point |
325.3ºC
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| Vapour Pressure |
1.11E-16mmHg at 25°C
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| LogP |
5.946
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
607
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CN(C[C@@H]1C(C2=CC=CC=C2)(C3=CC=CC=C3)C(=O)N)CCC4=CC5=C(C=C4)OCC5.Br
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| InChi Key |
UQAVIASOPREUIT-VQIWEWKSSA-N
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| InChi Code |
InChI=1S/C28H30N2O2.BrH/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);1H/t25-;/m1./s1
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| Chemical Name |
2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide hydrobromide
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| Synonyms |
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.93 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 (4.93 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 (4.93 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 | 1.9706 mL | 9.8530 mL | 19.7060 mL | |
| 5 mM | 0.3941 mL | 1.9706 mL | 3.9412 mL | |
| 10 mM | 0.1971 mL | 0.9853 mL | 1.9706 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00800462 | Completed | Drug: Oxybutynin Cl Drug: Trospium Cl Drug: Darifenacin Hydrogen Bromide (HBr) |
Spinal Cord Injury Neurogenic Detrusor Overactivity |
Toronto Rehabilitation Institute | March 2008 | Phase 4 |
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