| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Muscarinic acetylcholine receptors (mAChRs), particularly M1 and M3 subtypes located on salivary glands. Cevimeline acts as a muscarinic receptor agonist, binding to and activating muscarinic receptors on salivary gland acinar cells. This activation stimulates the production and secretion of saliva through intracellular signaling pathways involving phospholipase C and calcium mobilization. The compound exhibits selectivity for M1 and M3 receptors over M2 and M4 subtypes, which contributes to its favorable therapeutic profile with reduced cardiac and other off-target effects.
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| ln Vitro |
Cevimeline (0.1-100 μM) raises the intracellular Ca2+ content in parotid gland cells that have been digested [1].
In vitro studies demonstrate that Cevimeline is a potent muscarinic receptor agonist. The compound binds to muscarinic receptors with high affinity and activates downstream signaling pathways. In vitro functional assays measure receptor-mediated calcium mobilization or phosphoinositide hydrolysis in cells expressing muscarinic receptor subtypes. Cevimeline has been shown to stimulate salivary gland epithelial cells in culture, increasing intracellular calcium levels and promoting fluid secretion. The compound's IC50 values for muscarinic receptor binding have been determined in radioligand binding studies using membrane preparations from various tissues. |
| ln Vivo |
The administration of cevimeline (0.008-0.016 mg/kg; i.p.; Arsenal Wistar Blood Pressure) resulted in a gradual rise and persistence of dead fluid, along with a rise in adrenal blood flow and an elevation in pressure response. At 0.016 mg/kg, cevimeline reduces vascular tone.
In vivo studies in animal models and humans have demonstrated Cevimeline's efficacy in stimulating salivary secretion. In rat and dog models, oral administration of the compound resulted in rapid absorption and significant increases in salivary flow. Clinical studies in patients with Sjögren's syndrome showed that Cevimeline significantly improved symptoms of dry mouth compared to placebo. The compound's effects on other muscarinic receptor-mediated functions (e.g., gastrointestinal motility, urinary bladder function) have also been characterized in preclinical pharmacological studies. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Cevimeline typically use radioligand binding techniques with membrane preparations from tissues or cells expressing muscarinic receptor subtypes. The compound's affinity for M1, M2, M3, M4, and M5 receptors is determined by competition binding experiments using [3H]-N-methylscopolamine or [3H]-quinuclidinyl benzilate as radioligands. Membranes are incubated with varying concentrations of Cevimeline and a fixed concentration of radioligand. Non-specific binding is determined in the presence of excess atropine. After incubation, bound and free radioligands are separated by filtration, and radioactivity is counted. IC50 and Ki values are calculated from competition curves.
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| Cell Assay |
In vitro cell-based assays for Cevimeline use cell lines expressing muscarinic receptor subtypes (e.g., CHO cells transfected with human M1-M5 receptors). Cells are loaded with calcium-sensitive fluorescent dyes (e.g., Fluo-4) and stimulated with varying concentrations of Cevimeline. Intracellular calcium mobilization is measured using fluorescence plate readers. The compound's agonistic activity is determined by the increase in fluorescence intensity, and EC50 values are calculated from dose-response curves. Antagonist activity can be assessed by pre-incubating cells with Cevimeline followed by stimulation with a standard muscarinic agonist such as carbachol.
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| Animal Protocol |
Animal/Disease Models: Male Wistar rats (8 weeks old) injected with angiotensin-II[1]
Doses: 0.008mg/kg, 0.016mg/Angiotensin-II-induced water in the subfornical organ recognition and neuronal activity[1]. kg Mode of Route of Administration: intraperitoneal (ip) injection Experimental Results: Slow and sustained increase in salivation, increased parotid gland blood flow and increased pressor response. In vivo animal studies for Cevimeline are conducted in rats and dogs. In a typical pharmacokinetic study, animals receive a single oral or intravenous dose of the compound (e.g., 1-10 mg/kg). Blood samples are collected at various time points post-administration, and plasma concentrations are measured using liquid chromatography/mass spectrometry (LC/MS). Salivary secretion is measured by collecting saliva from anesthetized animals following compound administration. In pharmacological studies, various physiological parameters including heart rate, blood pressure, gastrointestinal motility, and urinary function are monitored to assess the compound's general pharmacological profile. |
| ADME/Pharmacokinetics |
Pharmacokinetics of Cevimeline have been extensively characterized in preclinical species and humans. After oral administration, the compound is rapidly absorbed with a mean time to peak concentration (Tmax) of 1.5 to 2 hours in humans. Plasma concentrations reach Cmax within 1 hour in rats and dogs. The bioavailability is approximately 50% in rats and 30% in dogs. The elimination half-life (t1/2) is 0.4-1.1 hours. Major metabolites in plasma include both S- and N-oxidized metabolites in rats, and only N-oxidized metabolite in dogs, indicating significant species differences in metabolism. Sulfoxidation is mediated by cytochrome P450 (CYP2D and CYP3A), while N-oxidation is mediated by flavin-containing monooxygenase (FMO). No accumulation of active drug or metabolites is observed following multiple-dose administration.
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| Toxicity/Toxicokinetics |
Toxicological data for Cevimeline have been generated from preclinical safety studies. The compound is generally well-tolerated at therapeutic doses in humans. Common adverse effects are related to muscarinic receptor activation and include sweating, nausea, rhinitis, and diarrhea. In preclinical toxicity studies, the compound has been evaluated for effects on general behavior, central nervous system, gastrointestinal, urinary, and reproductive systems. No significant genotoxicity or carcinogenicity has been reported at therapeutic doses. The compound is approved for clinical use in the treatment of xerostomia in Sjögren's syndrome.
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| References | |
| Additional Infomation |
Cevimeline hydrochloride is a cholinergic analogue with glandular secretion-stimulating activity. Cevimeline binds to and activates muscarinic receptors, thereby increasing the secretion of exocrine salivary and sweat glands. This cholinergic agonist also enhances the tone of smooth muscle in the gastrointestinal and urinary tracts. Currently, cevimeline is being investigated for the treatment of xerostomia caused by radiation therapy to the head and neck.
See also: Cevimeline hydrochloride (note moved to). Cevimeline hydrochloride hemihydrate is an FDA-approved therapeutic agent for the treatment of xerostomia (dry mouth) in patients with Sjögren's syndrome. It is available as an oral capsule formulation (30 mg). The drug is a muscarinic receptor agonist that stimulates salivary gland secretion. Its chemical structure is (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine]monohydrochloride hemihydrate with a molecular weight of 244.78. The compound is classified as a novel muscarinic receptor agonist developed specifically for xerostomia in Sjögren's syndrome. Clinical trials have demonstrated its efficacy and safety in improving dry mouth symptoms. The drug is typically administered three times daily with meals. |
| Molecular Formula |
2(C10H17NOS).2(HCL).H2O
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|---|---|
| Molecular Weight |
489.56
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| Exact Mass |
488.17
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| CAS # |
153504-70-2
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| Related CAS # |
Cevimeline hydrochloride;107220-28-0;(+)-Cevimeline hydrochloride hemihydrate;(-)-Cevimeline hydrochloride hemihydrate;Cevimeline;107233-08-9
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| PubChem CID |
73416227
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| Appearance |
White to off-white solid powder
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| Density |
1.19g/cm3
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| Boiling Point |
308.5ºC at 760mmHg
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| Flash Point |
140.4ºC
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| Vapour Pressure |
0.000676mmHg at 25°C
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| LogP |
4.535
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
29
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| Complexity |
215
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C[C@H]1O[C@@]2(CN3CCC2CC3)CS1.C[C@H]1O[C@@]2(CN3CCC2CC3)CS1.O.Cl.Cl
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| InChi Key |
ZSTLCHCDLIUXJE-ZGBAEQJLSA-N
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| InChi Code |
InChI=1S/2C10H17NOS.2ClH.H2O/c2*1-8-12-10(7-13-8)6-11-4-2-9(10)3-5-11;;;/h2*8-9H,2-7H2,1H3;2*1H;1H2/t2*8-,10-;;;/m00.../s1
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| Chemical Name |
(2S,5S)-2-methylspiro[1,3-oxathiolane-5,3'-1-azabicyclo[2.2.2]octane];hydrate;dihydrochloride
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| Synonyms |
AF-102B AF 102BSNK-508AF102B SNI2011 SNK508 AF-102B,SNK 508FKS-508 SNI-2011FKS508 SNI 2011 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 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) |
DMSO : ~100 mg/mL (~408.53 mM)
H2O : ≥ 50 mg/mL (~204.27 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.21 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 (10.21 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 (10.21 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: 100 mg/mL (408.53 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 | 2.0427 mL | 10.2133 mL | 20.4265 mL | |
| 5 mM | 0.4085 mL | 2.0427 mL | 4.0853 mL | |
| 10 mM | 0.2043 mL | 1.0213 mL | 2.0427 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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