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Purity: ≥98%
Solifenacin succinate (formerly YM-905; YM905; Trade name: Vesikur; Vesicare), the succinate salt of solifenacin which is approved for treating overactive bladder, is a novel and potent muscarinic receptor antagonist with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively.
| Targets |
Muscarinic M3 receptor (Ki = 0.4 nM) [2][3]
- Muscarinic M1 receptor (Ki = 3.0 nM) [2][3] - Muscarinic M2 receptor (Ki = 49 nM) [2][3] - Muscarinic M4 receptor (Ki = 14 nM) [2][3] - Muscarinic M5 receptor (Ki = 1.2 nM) [2][3] |
|---|---|
| ln Vitro |
Solifenacin Succinate (YM905) is a new type of muscarinic receptor antagonist. Its pKis for M1, M2, and M3 receptors are 7.6±0.056, 6.9±0.034, and 8.0±0.021, respectively. The antagonistic effects of oxybutynin and 100 nM solifenacin succinate on Ca2+ mobilization induced by different doses of carbachol (CCh) are investigated in murine submandibular gland cells. While oxybutynin exhibits unbreakable antagonistic interactions, solifenacin succinate does not alter the CCh dose-activation curve in a parallel fashion. For Solifenacin Succinate, the pKb values are 7.4±0.17 and for Oxybutynin, 8.8±0.21[1].
Solifenacin succinate (YM905) exhibits high selectivity for muscarinic M3 receptors, with a Ki of 0.4 nM, and lower affinity for M1 (3.0 nM), M4 (14 nM), M5 (1.2 nM), and M2 (49 nM) receptors [2][3] - In isolated guinea pig bladder smooth muscle strips, Solifenacin succinate (0.1–100 nM) dose-dependently inhibited acetylcholine (ACh)-induced contractions, with an IC50 of 1.6 nM. It showed 30-fold higher potency in bladder than in ileum (IC50 = 48 nM), indicating bladder selectivity [2] - In human bladder smooth muscle cells, the compound (1–100 nM) suppressed ACh-induced intracellular calcium mobilization, with a maximum inhibition rate of 82% at 100 nM [2] |
| ln Vivo |
At 210 nmol/kg (0.1 mg/kg), solifenacin succinate (YM905) decreases bladder reflexes by 40%, and at 2100 nmol/kg (1 mg/kg), it completely eliminates them. On the other hand, at 630 nmol/kg (0.3 mg/kg), its inhibitory effects on salivary and cardiac responses are negligible, and at 2100 nmol/kg (1 mg/kg), they increase to 66% and 49%, respectively. Saliva secretion is marginally increased by solifenacin succinate at dosages of 63 and 210 nmol/kg (0.03 and 0.1 mg/kg)[1]. At dosages of 0.03 mg/kg iv or higher, solifenacin succinate (0.01 to 0.3 mg/kg iv) improves bladder capacity and voided volume in a dose-dependent manner; however, residual volume and micturition pressure are unaffected at any tested dose[2].
In a rat model of bladder overactivity induced by partial bladder outlet obstruction, oral administration of Solifenacin succinate (0.3, 1, 3 mg/kg) dose-dependently improved voiding parameters. At 3 mg/kg, the number of voids was reduced by 45%, voided volume per micturition was increased by 52%, and residual urine volume was decreased by 60% compared to the control group [2] - In spontaneously hypertensive rats (SHR) with cold stress-induced detrusor overactivity, Solifenacin succinate (1 mg/kg, p.o.) alone reduced the frequency of non-voiding contractions by 38%. When combined with a β3-adrenergic agonist (10 mg/kg, p.o.), the inhibition rate increased to 65%, showing a synergistic effect [5] - In a clinical trial of Korean patients with overactive bladder, oral Solifenacin succinate (5 mg or 10 mg once daily for 12 weeks) significantly reduced the mean number of daily micturitions (from 12.8 to 8.3 in the 10 mg group) and urgency episodes (from 8.5 to 3.2 in the 10 mg group). The mean 24-hour urine volume per micturition increased by 35% [4] |
| Enzyme Assay |
Radioligand binding assay for muscarinic receptor subtypes: Recombinant human muscarinic receptors (M1–M5) were expressed in HEK293 cells, and cell membranes were prepared. Serial dilutions of Solifenacin succinate (0.01–1000 nM) were mixed with membrane suspensions and [3H]-N-methylscopolamine (a non-selective muscarinic ligand) in assay buffer. The mixture was incubated at 25°C for 60 minutes, and unbound ligands were removed by filtration. Radioactivity of the bound ligands was measured using a liquid scintillation counter, and Ki values were calculated using the Cheng-Prusoff equation [2][3]
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| Cell Assay |
Human bladder smooth muscle cells were seeded in 96-well plates and loaded with a fluorescent calcium indicator for 1 hour at 37°C. Cells were pretreated with Solifenacin succinate (1–100 nM) for 30 minutes, then stimulated with acetylcholine (10 μM) to induce calcium mobilization. Fluorescence intensity was monitored continuously for 60 seconds using a microplate reader, and the inhibition rate of calcium response was calculated [2]
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| Animal Protocol |
0.01 to 0.3 mg/kg; i.v.
Male rats Rat partial bladder outlet obstruction model: Male SD rats underwent partial ligation of the bladder neck to induce overactive bladder. Two weeks post-surgery, rats were randomly divided into control (saline) and Solifenacin succinate groups (0.3, 1, 3 mg/kg, p.o., n=8 per group). Drugs were administered once daily for 7 days, and voiding parameters (voiding frequency, voided volume, residual urine) were measured using metabolic cages [2] - SHR cold stress-induced detrusor overactivity model: Spontaneously hypertensive rats were acclimated to metabolic cages, then exposed to cold stress (4°C) for 2 hours to induce detrusor overactivity. Rats were treated with Solifenacin succinate (1 mg/kg, p.o.), β3-agonist (10 mg/kg, p.o.), or their combination 1 hour before cold exposure. Voiding frequency and non-voiding contractions were recorded during the stress period [5] |
| ADME/Pharmacokinetics |
Solifenacin succinate has an oral bioavailability of approximately 88% in humans [3] - After oral administration of 5 mg, the peak plasma concentration (Cmax) is 32.3 ng/mL, the time to peak concentration (Tmax) is 3-8 hours, and the plasma half-life (t1/2) is approximately 50 hours [3] - This compound is widely distributed with a distribution volume of 600 L. It has a high binding rate to human plasma proteins (98%) [3] - It is mainly metabolized in the liver by cytochrome P450 3A4 (CYP3A4) to inactive metabolites. Approximately 70% of the dose is excreted in the urine (13% of which is the original drug) and 30% is excreted in the feces [3]
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Since there are currently no reported studies on the use of solifenacin during lactation, and its half-life is relatively long (average 55 hours), it is recommended to prioritize other medications, especially when breastfeeding newborns or premature infants. Long-term use of solifenacin may reduce milk production or inhibit the milk ejection reflex. During long-term use, the infant should be monitored for signs of reduced milk production (e.g., satiety, poor weight gain) and anticholinergic symptoms (e.g., constipation, urinary retention, urinary tract infection, dry mouth). ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk Anticholinergic drugs may inhibit lactation in animals by suppressing the secretion of growth hormone and oxytocin. Anticholinergic drugs may also reduce serum prolactin levels in non-lactating women. Prolactin levels in established lactating mothers may not affect their ability to breastfeed. Common clinical adverse reactions include dry mouth (23%–30% of patients), constipation (10%–15%), blurred vision (5%–8%), and urinary retention (1%–2%). These adverse reactions are mild to moderate and reversible.[3][4] - No significant hepatotoxicity or nephrotoxicity was observed in clinical trials, and there were no consistent changes in serum ALT, AST, creatinine, or blood urea nitrogen levels.[3][4] - Solifenacin succinate may interact with CYP3A4 inhibitors (e.g., ketoconazole), increasing its plasma concentration by up to 2.5 times.[3] - The oral LD50 in rats is >2000 mg/kg, indicating low acute toxicity.[3] |
| References |
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| Additional Infomation |
Solifenacin succinate belongs to the isoquinoline class of compounds. It is a quinine ring and tetrahydroisoquinoline derivative and a selective M3 muscarinic receptor antagonist. It is used as a urological drug to treat urinary incontinence. See also: Solifenacin (containing the active ingredient).
Drug indication Treatment of neurogenic detrusor overactivity Solifenacin succinate (YM905) is a bladder-selective anticholinergic drug primarily used to treat overactivity of the bladder with symptoms of urinary urgency, frequency and nocturia[2][3][4] - Its mechanism of action involves competitive antagonism of muscarinic M3 receptors in the detrusor muscle of the bladder, inhibiting acetylcholine-induced contractions, thereby reducing bladder overactivity[2][3] - Its high selectivity for the bladder relative to other tissues (e.g., the gastrointestinal tract) is attributed to its higher potency to muscarinic receptors in bladder smooth muscle. Compared with intestinal smooth muscle receptors [2] - The clinical dose range is 5 mg to 10 mg once daily, and no dose adjustment is required for elderly patients (≥65 years) or patients with mild to moderate renal impairment [3][4] |
| Molecular Formula |
C23H26N2O.C4H6O4
|
|---|---|
| Molecular Weight |
480.55
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| Exact Mass |
480.226
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| CAS # |
242478-38-2
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| Related CAS # |
Solifenacin;242478-37-1;Solifenacin hydrochloride;180468-39-7;Solifenacin D5 hydrochloride;1426174-05-1;Solifenacin-d5 succinate
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| PubChem CID |
216457
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| Appearance |
White to off-white solid powder
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| Density |
1.24g/cm3
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| Boiling Point |
505.5ºC at 760 mmHg
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| Melting Point |
147 °C
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| Flash Point |
259.5ºC
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| Vapour Pressure |
2.41E-10mmHg at 25°C
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| Index of Refraction |
1.648
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| LogP |
3.676
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
617
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CN2CCC1[C@H](C2)OC(=O)N3CCC4=CC=CC=C4[C@@H]3C5=CC=CC=C5.C(CC(=O)O)C(=O)O
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| InChi Key |
RXZMMZZRUPYENV-VROPFNGYSA-N
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| InChi Code |
InChI=1S/C23H26N2O2.C4H6O4/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;5-3(6)1-2-4(7)8/h1-9,18,21-22H,10-16H2;1-2H2,(H,5,6)(H,7,8)/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;butanedioic acid
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| Synonyms |
YM 905 succinate; Solifenacin succinate; YM-905; YM905; Trade name: Vesikur; Vesicare.
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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. |
| 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 (5.20 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 (5.20 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 (5.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (104.05 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0809 mL | 10.4047 mL | 20.8095 mL | |
| 5 mM | 0.4162 mL | 2.0809 mL | 4.1619 mL | |
| 10 mM | 0.2081 mL | 1.0405 mL | 2.0809 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.
A Clinical Study to Investigate How Solifenacin Fluid is Taken up, How Long it Stays in the Body and How Effective and Safe it is in Treating Children Aged From 6 Months to Less Than 5 Years With Symptoms of Neurogenic Detrusor Overactivity (NDO)
CTID: NCT01981954
Phase: Phase 3 Status: Completed
Date: 2024-10-31
Products are for research use only; We do not sell to patients
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