| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| 2g |
|
||
| 10g |
|
||
| Other Sizes |
|
Purity: ≥98%
Solifenacin (YM-905; Vesikur; Vesicare) is a novel and potent muscarinic receptor antagonist that has been approved for the treatment of overactive bladder. It blocks muscarinic M1, M2 and M3 receptors with pKis of 7.6, 6.9 and 8.0, respectively.
| Targets |
M1 receptor ( Kd = 2.9 nM ); M2 receptor ( Kd = 6.9 ); M3 receptor ( Kd = 8.0 )
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Cell Assay |
In guinea pig detrusor cells, the mobilization of cytosolic Ca2+ is measured. In summary, phenol red-free Hanks' balanced salt solution supplemented with 20 mM HEPES (pH=7.4) and 0.1% bovine serum albumin (HBSS-H/B) is used to prepare single detrusor cells from epithelium-free bladders, load them with Fura 2, and suspend them in the solution. A 490 μL portion of the cell suspension is constantly mixed, maintained at 28°C, and observed for the ratio of fluorescence at 500 nm to that at 380 nm when excited at 340 nm. Five microliters of test drug (such as Solifenacin) and stimulant solutions are successively added to each aliquot at intervals of two minutes. The peak increase over the level immediately prior to stimulation is utilized for data analysis[1].
|
|
| Animal Protocol |
|
|
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Solifenacin is well absorbed in the duodenum, jejunum, and ileum but not the stomach. Absorption occurs via passive diffusion and so no transporters are involved. The mean oral bioavailability of solifenacin is 88%. The Tmax of solifenacin is 3-8 hours with a Css of 32.3ng/mL for a 5mg oral dose and 62.9ng/mL for a 10mg oral dose. 69.2±7.8% of a radiolabelled dose is recovered in the urine, 22.5±3.3% was recovered in feces, and 0.4±7.8% was recovered in exhaled air. 18% of solifenacin is eliminated as the N-oxide metabolite, 9% is eliminated as the 4R-hydroxy N-oxide metabolite, and 8% is eliminated as the 4R-hydroxy metabolite. The volume of distribution of solifenacin is 600L. The clearance of solifenacin is 7-14L/h and a renal clearance of 0.67-1.51L/h. Metabolism / Metabolites Solifenacin undergoes N-oxidation at the quinuclidin ring by cytochrome P450, though the exact enzymes are not revealed in the literature. The tetrahydroisoquinolone ring is 4R-hydroxylated by CYP3A4, CYP1A1, and CYP2D6. A 4R-hydroxy N-oxide metabolite is also formed by CYP3A4. Finally, solifenacin can undergo direct glucuronidation. Only solifenacin and the 4R-hydroxy metabolite are pharmacologically active. Biological Half-Life The elimination half life of solifenacin ranges from 33-85 hours. |
|
| Toxicity/Toxicokinetics |
Hepatotoxicity
Like most anticholinergic agents, solifenacin has not been linked to liver enzyme elevations during therapy or to instances of clinically apparent liver injury with jaundice. In multiple prospective clinical trials of solifenacin in patients with overactive bladder syndrome, ALT elevations were reported in less than 1% of treated subjects, rates similar to that of placebo-recipients. Despite widespread clinical use for almost two decades, there has been only a single published case report of possible liver injury due to darifenacin use. An elderly woman with end stage liver injury developed transient elevations of serum aminotransferases and alkaline phosphatase without jaundice two weeks after starting solifenacin. Thus, liver injury due to solifenacin must be rare if it occurs at all. Likelihood score: D (possible, very rare cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Because there is no published experience with solifenacin during breastfeeding and it has a long half-life averaging 55 hours, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Long-term use of solifenacin might reduce milk production or milk letdown. During long-term use, observe the infant for signs of decreased milk production (e.g., insatiety, poor weight gain) and for anticholinergic symptoms (e.g., constipation, urinary retention, UTI, dry mouth). ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Anticholinergics can inhibit lactation in animals, apparently by inhibiting growth hormone and oxytocin secretion. Anticholinergic drugs can also reduce serum prolactin in nonnursing women. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Protein Binding Solifenacin is 93-96% protein bound in plasma, mainly to alpha-1-acid glycoprotein. |
|
| References |
|
|
| Additional Infomation |
Solifenacin is a member of isoquinolines.
Solifenacin is a competitive muscarinic receptor antagonist indicated to treat an overactive bladder with urinary incontinence, urgency, and frequency. It has a long duration of action as it is usually taken once daily. Solifenacin was granted FDA approval on 19 November 2004. Solifenacin is a Cholinergic Muscarinic Antagonist. The mechanism of action of solifenacin is as a Cholinergic Muscarinic Antagonist. Solifenacin is an anticholinergic and antispasmodic agent used to treat urinary incontinence and the overactive bladder syndrome. Solifenacin has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury. A quinuclidine and tetrahydroisoquinoline derivative and selective M3 MUSCARINIC ANTAGONIST. It is used as a UROLOGIC AGENT in the treatment of URINARY INCONTINENCE. See also: Solifenacin Succinate (has salt form). Drug Indication Solifenacin tablets are indicated to treat an overactive bladder with urinary incontinence, urgency, and frequency. FDA Label Mechanism of Action Solifenacin is a competitive muscarinic receptor antagonist. It has the highest affinity for M3, M1, and M2 muscarinic receptors. 80% of the muscarinic receptors in the bladder are M2, while 20% are M3. Solifenacin's antagonism of the M3 receptor prevents contraction of the detrusor muscle, while antagonism of the M2 receptor may prevent contraction of smooth muscle in the bladder. Pharmacodynamics Solifenacin antagonizes the M2 and M3 muscarinic receptors in the bladder to treat an overactive bladder. It has a long duration of action as it is usually taken once daily. Patients taking solifenacin should be aware of the risks of angioedema and anaphylaxis. |
| Molecular Formula |
C23H26N2O2
|
|---|---|
| Molecular Weight |
362.46
|
| Exact Mass |
362.199
|
| CAS # |
242478-37-1
|
| Related CAS # |
Solifenacin Succinate; 242478-38-2; Solifenacin hydrochloride; 180468-39-7; Solifenacin D5 hydrochloride; 1426174-05-1
|
| PubChem CID |
154059
|
| Appearance |
White to off-white solid
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
505.5±50.0 °C at 760 mmHg
|
| Melting Point |
134-136
|
| Flash Point |
259.5±30.1 °C
|
| Vapour Pressure |
0.0±1.3 mmHg at 25°C
|
| Index of Refraction |
1.649
|
| LogP |
3.7
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
27
|
| Complexity |
525
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
O=C(O[C@@]1([H])C[N@]2CC[C@@H]1CC2)N3CCC4=CC=CC=C4[C@@H]3C5=CC=CC=C5
|
| InChi Key |
FBOUYBDGKBSUES-VXKWHMMOSA-N
|
| InChi Code |
InChI=1S/C23H26N2O2/c26-23(27-21-16-24-13-10-18(21)11-14-24)25-15-12-17-6-4-5-9-20(17)22(25)19-7-2-1-3-8-19/h1-9,18,21-22H,10-16H2/t21-,22-/m0/s1
|
| Chemical Name |
[(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
|
| Synonyms |
YM905; YM 905; YM-905; Solifenacin succinate; Trade name: Vesikur; Vesicare.
|
| 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 |
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.90 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 (6.90 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 (6.90 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 | 2.7589 mL | 13.7946 mL | 27.5893 mL | |
| 5 mM | 0.5518 mL | 2.7589 mL | 5.5179 mL | |
| 10 mM | 0.2759 mL | 1.3795 mL | 2.7589 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 |
| NCT01530373 | Active Recruiting |
Drug: solifenacin Drug: Clonidine |
Hot Flashes Breast Cancer |
University of Arkansas | February 2012 | Phase 2 |
| NCT05494567 | Active Recruiting |
Drug: Tadalafil 5mg Drug: solifenacin 10 mg |
Benign Prostatic Hyperplasia Overactive Bladder |
Mansoura University | November 8, 2021 | Phase 4 |
| NCT04023253 | Recruiting | Drug: Mirabegron Drug: Solifenacin |
Overactive Bladder Syndrome | Far Eastern Memorial Hospital | August 1, 2019 | Phase 3 |
| NCT05490082 | Completed | Drug: Mirabegron, Propevirine, Solifenacin |
Voiding Disorders | Mansoura University | March 1, 2022 | Phase 3 |
| NCT04819360 | Completed | Drug: VESIcare 10Mg Tablet Drug: Botox 100 UNT Injection |
Urinary Bladder, Neurogenic Multiple Sclerosis |
Brigitte Schürch | June 1, 2021 | Phase 4 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
MSDS