| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Cevimeline (FKS-508; SNI-2011; AF-102B; SNK-508; trade name Evoxac) is a potent parasympathomimetic and muscarinic agonist thas has been approved for use in the treatment of dry mouth and Sjögren's syndrome, as well as Xerostomia symptoms.
| ln Vitro |
Cevimeline (0.1-100 μM) raises the intracellular Ca2+ content in parotid gland cells that have been digested [1].
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|---|---|
| ln Vivo |
Male Wistar rats administered with cevimeline (0.008-0.016 mg/kg intraperitoneally) exhibited increased pressor response, increased salivation, and a gradual and sustained rise in parotid gland blood flow. In the subfornical organ, cevimeline, at 0.016 mg/kg, reduces angiotensin II-induced water intake and neuronal activity [1].
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| Animal Protocol |
Animal/Disease Models: Male Wistar rats (8 weeks old) were injected with angiotensin-II[1].
Doses: 0.008 mg/kg, 0.016 mg/kg. Route of Administration: intraperitoneal (ip) injection. Experimental Results: Salivation increased slowly and persistently, and blood flow increased. Increased in parotid and pressor responses. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Absorption is rapid, with peak concentration reached in 1.5 to 2 hours. 84% of a 30 mg dose of cevimeline is excreted in the urine after 24 hours. 6 L/kg Excretion: Urine: 97%. Feces: 0.5%. It is unknown whether this drug is excreted into human breast milk. Following a single 30 mg capsule dose, cevimeline is rapidly absorbed, with a mean time to peak concentration of 1.5 to 2 hours. No accumulation of the active drug or its metabolites has been observed after multiple doses. The absorption rate decreases when taken with food, with a peak time of 1.53 hours on an empty stomach and 2.86 hours after a meal; peak concentration is reduced by 17.3%. Within the clinical dose range, the single oral dose is dose-dependent. The volume of distribution of cevimeline is approximately 6 L/kg, and its binding to human plasma proteins is less than 20%. This indicates that cevimeline binds extensively to tissues; however, the specific binding sites are unknown. After 24 hours, 84% of the 30 mg dose of cevimeline was excreted in the urine. After 7 days, 97% of the dose was recovered in the urine and 0.5% in the feces. Metabolism/Metabolites Cevimeline is primarily metabolized in the liver, with CYP2D6 and CYP3A4 isoenzymes responsible for its metabolism. Approximately 44.5% of the drug is converted to cis and trans sulfoxides, 22.3% to glucuronide conjugates, and 4% to cevimeline N-oxides. Approximately 8% of the trans sulfoxide metabolites are subsequently converted to their corresponding glucuronide conjugates. This study investigated the pharmacokinetics and metabolism of cevimeline in six healthy volunteers following a single oral dose of 14(C)-cevimeline. ...Twenty-four hours after administration, the average recoveries of the metabolites in urine were as follows: cevimeline 16.0%, cevimeline trans sulfoxide 35.8%, cevimeline cis sulfoxide 8.7%, and cevimeline N-oxide 4.1%. In addition, two unknown metabolites, UK-1 and UK-2, were detected, with recoveries of 14.6% and 7.7%, respectively. Liquid chromatography-mass spectrometry analysis and hydrolysis studies showed that UK-1 and UK-2 are cevimeline glucuronide conjugate and cevimeline trans sulfoxide, respectively. CYP2D6 and CYP3A3/4 isoenzymes are responsible for the metabolism of cevimeline. After 24 hours, 86.7% of the dose was recovered (16.0% of the original drug, 44.5% of cis and trans sulfoxides, 22.3% of glucuronide conjugate, and 4% of cevimeline N-oxide). Approximately 8% of the trans-sulfoxide metabolites are subsequently converted to their corresponding glucuronide conjugates and excreted. Cevimeline does not inhibit cytochrome P450 isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4. Biological Half-Life 5±1 hours Elimination: Approximately 5 hours. The mean half-life of cevimeline is 5±1 hours. |
| Toxicity/Toxicokinetics |
Hepatotoxicity
In premarket trials of cevimeline, the incidence of elevated serum enzymes was not significantly different from the placebo group, and no reports of acute liver injury were observed. Since its market launch and wider use, cevimeline has not been associated with any clinically visible cases of liver injury. Probability Score: E (Unlikely to cause clinically visible liver injury). Protein Binding 20% Interactions Due to the possibility of conduction disturbances, cevimeline should be used with caution in patients taking β-adrenergic antagonists. Concomitant use of drugs with parasympathomimetic effects with cevimeline may have an additive effect. Cevimeline may interfere with the anticholinergic effects of concomitantly taken drugs. Drugs that inhibit CYP2D6 and CYP3A3/4 may also inhibit the metabolism of cevimeline. Based on past experience, individuals with known or suspected CYP2D6 deficiency should use cevimeline with caution, as they may have a higher risk of adverse events. |
| References | |
| Additional Infomation |
Cevimeline is a parasympathomimetic drug that acts as an agonist of muscarinic acetylcholine receptors M1 and M3. The U.S. Food and Drug Administration (FDA) has approved it for the treatment of dry mouth symptoms associated with Sjögren's syndrome. Cevimeline is an oral cholinergic agonist used to treat dry mouth symptoms in patients with dry keratoconjunctivitis (Sjögren's syndrome). No cases of elevated serum enzymes or clinically significant liver injury have been observed during treatment with cevimeline. Cevimeline is a cholinergic analogue that stimulates glandular secretion. It binds to and activates muscarinic receptors, thereby increasing the secretion of exocrine salivary and sweat glands. This cholinergic agonist also increases the tone of smooth muscle in the gastrointestinal and urinary tracts. Cevimeline is being investigated for the treatment of dry mouth induced by radiation therapy to the head and neck. Drug Indications: For the treatment of dry mouth symptoms in patients with Sjögren's syndrome.
FDA Label Mechanism of Action M then-and-sodium muscarinic receptor agonists bind to and activate muscarinic M1 and M3 receptors. M1 receptors are commonly found in secretory glands (such as salivary and sweat glands), and their activation leads to increased secretion. M3 receptors are present in smooth muscle and many glands, helping to stimulate salivary gland secretion; their activation typically leads to smooth muscle contraction and increased glandular secretion. Therefore, with increased saliva production, dry mouth symptoms are relieved. Cevimeline hydrochloride is a quinine ring derivative of acetylcholine and a cholinergic agonist that binds to muscarinic receptors. At adequate doses, muscarinic agonists can lead to increased secretion from exocrine glands (such as sweat and salivary glands) and increased smooth muscle tone in the gastrointestinal and urinary tracts. Cevimeline has a higher affinity for muscarinic receptors on the epithelial cells of lacrimal and salivary glands than for those on myocardial tissue. Cevimeline's structure is unrelated to other existing drugs, but its pharmacological action is similar to pilocarpine, another oral cholinergic agonist that primarily acts as a muscarinic. Both drugs stimulate damaged but still functional residual salivary gland tissue. Therapeutic Use Cevimeline is indicated for the treatment of dry mouth, a common symptom of Sjögren's syndrome. /US Product Label Contains/ Drug Warnings FDA Pregnancy Risk Class: C/Risk cannot be ruled out. Adequate, well-controlled human studies are lacking, and animal studies have not shown any risk to the fetus or lack relevant data. Use of this drug during pregnancy may cause harm to the fetus; however, the potential benefits may outweigh the potential risks. / The safety and efficacy of cevimeline in the treatment of Alzheimer's disease dementia have not been established. Use of cevimeline may cause excessive sweating and may lead to dehydration. If this occurs, patients should drink plenty of water and consult a doctor. There is a risk of changes in cardiac conduction and/or heart rate. Patients with clinically significant cardiovascular disease may not be able to compensate for transient hemodynamic or cardiac rhythm changes caused by cevimeline. Patients with a history of cardiovascular disease (e.g., angina, myocardial infarction) should use this medication with caution and under close medical supervision. For more complete data on cevimeline (14 in total), please visit the HSDB record page. Pharmacodynamics Cevimeline is a cholinergic agonist that binds to muscarinic receptors. Sufficient doses of muscarinic agonists can increase the secretion of exocrine glands such as salivary and sweat glands, and increase the tone of smooth muscle in the gastrointestinal and urinary tracts. |
| Molecular Formula |
C10H17NOS
|
|---|---|
| Molecular Weight |
199.31
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| Exact Mass |
199.1031
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| CAS # |
107233-08-9
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| Related CAS # |
Cevimeline hydrochloride;107220-28-0;Cevimeline hydrochloride hemihydrate;153504-70-2;(+)-Cevimeline hydrochloride hemihydrate
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| PubChem CID |
2684
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
308.5±42.0 °C at 760 mmHg
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| Melting Point |
195-197ºC
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| Flash Point |
140.4±27.9 °C
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| Vapour Pressure |
0.0±0.7 mmHg at 25°C
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| Index of Refraction |
1.586
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| LogP |
1.23
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
|
| Heavy Atom Count |
13
|
| Complexity |
215
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
S1[C@]([H])(C([H])([H])[H])O[C@@]2(C1([H])[H])C([H])([H])N1C([H])([H])C([H])([H])C2([H])C([H])([H])C1([H])[H]
|
| InChi Key |
WUTYZMFRCNBCHQ-WPRPVWTQSA-N
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| InChi Code |
1S/C10H17NOS/c1-8-12-10(7-13-8)6-11-4-2-9(10)3-5-11/h8-9H,2-7H2,1H3/t8-,10-/m0/s1
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| Chemical Name |
Spiro(1-azabicyclo(2.2.2)octane-3,5'-(1,3)-oxathiolane), 2'-methyl-, (2'R,3R)-rel-
|
| Synonyms |
FKS508 SNI 2011AF-102BSNK 508FKS-508 SNI-2011AF 102BSNK-508AF102B SNI2011 SNK508 AF-102B, Cevimeline, FKS 508, HSDB 7286, SNI 2011
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.0173 mL | 25.0865 mL | 50.1731 mL | |
| 5 mM | 1.0035 mL | 5.0173 mL | 10.0346 mL | |
| 10 mM | 0.5017 mL | 2.5087 mL | 5.0173 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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