Description
Solifenacin succinate is an antimuscarinic medication that is used to treat an overactive bladder causing symptoms of frequency, urgency, or incontinence.
Proper Usage
- This medication should be taken with liquids and swallowed whole. It may be taken with or without food.
- Take only the amount of this medication that has been prescribed for you by your doctor; taking more than the prescribed amount can cause adverse effects.
- If you miss a dose of this medication, begin taking it again the next day. Do not take two doses of solifenacin succinate in the same day.
Precautions
- Individuals with any of the following medical problems should not take this medication: urinary retention, gastric retention, narrow angle or uncontrolled glaucoma, or severe kidney problems. Solifenacin succinate can aggravate each of these conditions.
- Solifenacin succinate may cause blurred vision; do not engage in potentially dangerous activities such as driving until you know the effect of the medication on your vision.
- This medication, like all anticholinergic medications, may cause drying of the mouth. Since continued dryness of the mouth can increase the risk of dental disease, alert your dentist if you are taking this medication.
- Like all anticholinergic medications, solifenacin succinate can cause or worsen constipation.
- Because of decreased sweating, this medication can cause heat prostration when used in a very hot environment.
- This medication has not been studied in pregnant women. However, it has been shown in animal studies to impact preand postnatal development. If you are pregnant, or planning to become pregnant, do not start this medication before you have discussed it with your physician.
- It is not known whether solifenacin succinate passes into breast milk. Women who taking this medication and wish to breastfeed should discuss it with their physician.
Possible Side effects
- Side effects that are expected with this type of medication and do not require medical attention unless they continue or are bothersome: dry mouth; dry eyes; constipation, blurred vision, difficult urination.
- Less common side effect that should be reported to your physician: severe abdominal pain.
- Symptoms of overdose: severe central anticholinergic effects, including blurred vision; clumsiness or unsteadiness; confusion; seizures; severe diarrhea; excessive watering of the mouth; increasing 240 Multiple Sclerosis: A Self-Care Guide to Wellness muscle weakness (especially in the arms, neck, shoulders, and tongue); muscle cramps or twitching; severe nausea or vomiting; shortness of breath; slow heartbeat; slurred speech; unusual irritability, nervousness, or restlessness; unusual tiredness or weakness.
Description
Solifenacin is an M3 muscarinic receptor antagonist that was developed and
launched for the treatment of overactive bladder (pollakiuria) in Europe. M3 receptors
have been implicated in neurally evoked smooth muscle contractions of the
bladder, and M2 receptors have also been suspected of playing a role because of
their dominance in the detrusor muscle. Solifenacin displays affinity for both M3
and M2 receptors with K
i values of 9.9nM and 120 nM, respectively. Since muscarinic
salivary glands are of the M3 persuasion, a common side effect of antimuscarinic
therapy is dry mouth. At the cellular level, solifenacin possesses a selective
preference for bladder over salivary gland that is 15-fold greater than that of atropine
suggesting a lower probability of inducing dry mouth at pharmacologically relevant
doses. The synthesis of solifenacin involves the preparation of racemic 1-phenyl-
1,2,3,4-tetrahydroisoquinoline via cyclization of N-(2-phenylethyl)benzamide, and
subsequent reaction with ethyl chloroformate and transesterification with (R)-
3-quinuclidinol. Chiral chromatography affords the isolation of the desired diastereomer.
Alternatively, 1-phenyl-1,2,3,4-tetrahydroisoquinoline may be subjected
to optical resolution with (+)-tartaric acid prior to treatment with ethyl chloroformate
and subsequent transesterification. The pooled results of four phase III trials
concluded that 63% of women receiving 5mg of solifenacin once daily and 68% of
women receiving 10mg once daily reported a 50% or more reduction in urgency
episodes, compared to 44% of women taking placebo. This compares with a 53%
reduction in patients receiving tolterodine twice daily. In another placebo-controlled
trial, with the change in the number of micturitions in a 24-h period as the primary
endpoint, once-daily solifenacin recorded an 18% decrease for a 5-mg dose and a
21% decrease for a 10-mg dose compared to 10% with placebo. Pharmacokinetic
studies have demonstrated that solifenacin has an oral bioavailability of 90%, a long
elimination half-life (50 h), low clearance (9.39 L/h), a mean V
ss of 599 L, a C
max of
approximately 14 ng/mL, and a time to maximal plasma concentration of 4 h making
it suitable for q.d. dosing. Furthermore, these PK parameters are not affected by food
ingestion. Solifenacin is excreted predominantly in the feces with only 3–6% found in urine. It is contraindicated in patients with hepatic impairment, gastric retention,
urinary retention, or uncontrolled narrow angle glaucoma. Further precautions, such
as dose adjustment, should be considered for patients with concurrent use of
ketoconazole or other potent CYP3A4 inhibitors or for patients with a history of QT
prolongation or currently on medications known to prolong the QT interval. Finally,
while other muscarinic antagonists have been explored in the treatment of irritable
bowel syndrome (IBS), it is too early to predict the therapeutic utility of solifenacin
for IBS although animal studies are promising.
Chemical Properties
White Solid
Originator
Yamanouchi (Japan)
Uses
Muscarinic M3 receptor antagoinst. Used in treatment of urinary incontinence.
Uses
Solifenacin succinate is a urinary antispasmodic of the antimuscarinic class.
Definition
ChEBI: Solifenacin succinate is a member of isoquinolines.
brand name
Vesicare (Astellas).
Synthesis Reference(s)
[1]Kale, B. R., Hamid, H., & Alam, M. S. (2025). An Improved and Efficient Practical Process for the Synthesis of Enantiomerically Pure Solifenacin Succinate as an Antimuscarinic Agent. Current Organocatalysis, 12(1), 76–82.
https://doi.org/10.2174/0122133372336988240910104559 [2]Trinadhachari, G. N., Kamat, A. G., Balaji, B. V., Prabahar, K. J., Naidu, K. M., Babu, K. R., & Sanasi, P. D. (2014). An Improved Process for the Preparation of Highly Pure Solifenacin Succinate via Resolution through Diastereomeric Crystallisation. Organic Process Research & Development, 18(8), 934–940.
https://doi.org/10.1021/op500083y [3]Niphade, N. C., Jagtap, K. M., Mali, A. C., Solanki, P. V., Jachak, M. N., & Mathad, V. T. (2011). Efficient and single pot process for the preparation of enantiomerically pure solifenacin succinate, an antimuscarinic agent. Monatshefte für Chemie - Chemical Monthly, 142(11), 1181–1186.
https://doi.org/10.1007/s00706-011-0610-7
General Description
Solifenacin succinate (Vesicare),(+)-(1S, 3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate, is a competative antagonistfor M1, M2, and M3 receptor subtypes. One of the issues surroundingthe use of such antagonists is the selectivity for thebladder over other tissue such as the salivary glands. It isreported that the selectivity of solifenacin for bladder muscarinicreceptors over salivary receptors is superior to theeffects observed with oxybutynin.
Clinical Use
Selective M3
antimuscarinic
Symptomatic treatment of urge incontinence and/or
increased urinary frequency and urgency
Synthesis
Enantiomerically pure solifenacin succinate can be synthesized via a Zn(OTf)2-catalyzed protocol using phenylethylamine and benzoyl chloride as starting materials, or through a one-pot process that retains chiral center configuration[1][3]. Alternative preparation methods involve resolution of diastereomeric mixtures through crystallization, including optimization with specific solvent systems such as ethanol in ethyl acetate[2]. The final salt formation is achieved by treating solifenacin with succinic acid in acetone, involving heating to 50–55°C followed by cooling to isolate crystals with high chemical and enantiomeric purity[3].
in vitro
in radioligand receptor binding assay, the kivalues of solifenacin for human muscarinic m1, m2, m3, m4and m5receptors were 26, 170, 12, 110 and 31 nm, respectively. in isolated rat urinary bladder, solifenacin competitively antagonized carbachol-induced contractions, with a pa2value of 7.44±0.09[3].in bladder smooth muscle cells and salivary gland cells isolated from rats, solifenacin and the other antimuscarinic drugs inhibited carbachol-induced increases in intracellular ca2+levels in a concentration-dependent manner. thepki was 8.12for bladder smooth muscle cells, 3.6-fold more potent than that for salivary gland cells (pki=7.57) [1].
in vivo
in anesthetized rats, solifenacin dose-dependently inhibited carbachol-induced intravesical pressure elevation and salivary secretion, and exhibited selectivity (3.7- to 6.5-fold) for urinary bladder over salivary gland [1]. in anesthetized rats, solifenacin and oxybutynin increased the maximum bladder capacity in a dose-dependent manner and also decreased the maximum intravesical pressure [3].in healthy young men, multidose study evaluated doses. in the single-dose of solifenacin succinate (5-, 10-, 20-, and 30-mg), mean time to maximal concentration and elimination half-life ranged from 3.3 to 4.8 and from 40.2 to 57.6 hours, respectively.in the multidose study, the ranges were 2.9 to 5.8 and 45.0 to 64.8, respectively. the single-dose administration was well tolerated. the common adverse events were dry mouth, blurred vision, and headache [4].
Drug interactions
Potentially hazardous interactions with other drugs
Avoid if GFR<30 mL/min if also taking
itraconazole, ketoconazole or ritonavir.
Anti-arrhythmics: increased risk of antimuscarinic
side effects with disopyramide.
Metabolism
Extensively metabolised in the liver, mainly by the
cytochrome P450 isoenzyme CYP3A4 and is excreted
mainly as metabolites in urine and faeces.
References
[1]. ohtake a, ukai m, hatanaka t, et al. in vitro and in vivo tissue selectivity profile of solifenacin succinate (ym905) for urinary bladder over salivary gland in rats[j]. european journal of pharmacology, 2004, 492(2): 243-250.
[2]. yang j, williams j a, yule d i, et al. mutation of carboxyl-terminal threonine residues in human m3 muscarinic acetylcholine receptor modulates the extent of sequestration and desensitization[j]. molecular pharmacology, 1995, 48(3): 477-485.
[3]. ohtake a, saitoh c, yuyama h, et al. pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents[j]. biological and pharmaceutical bulletin, 2007, 30(1): 54-58.
[4]. smulders r a, krauwinkel w j, swart p j, et al. pharmacokinetics and safety of solifenacin succinate in healthy young men[j]. the journal of clinical pharmacology, 2004, 44(9): 1023-1033.
[5]. cardozo l, lisec m, millard r, et al. randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder[j]. the journal of urology, 2004, 172(5): 1919-1924.
