| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Muscarinic acetylcholine receptors (mAChR), specifically the M1 and M3 subtypes. These are G protein-coupled receptors that mediate secretory functions in exocrine glands (salivary, lacrimal, sweat). Activation of M1/M3 receptors on salivary gland acinar cells increases intracellular calcium, leading to fluid secretion.
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| ln Vitro |
In vitro, (+)-Cevimeline exhibits high affinity for muscarinic M1 and M3 receptors with Ki values in the low nanomolar range. It shows selectivity for M1 and M3 over M2 and M4 receptors. Functional assays demonstrate that it increases intracellular calcium and stimulates amylase secretion from salivary gland acinar cells.
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| ln Vivo |
In conscious rats and dogs, oral or subcutaneous administration of (+)-Cevimeline hydrochloride produces a marked and sustained increase in salivary flow (sialagogue effect). This effect is blocked by the muscarinic antagonist atropine. In vivo efficacy in Sjögren's syndrome models shows restoration of salivary function without significant cardiovascular effects at therapeutic doses.
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| Enzyme Assay |
Membrane preparations from CHO cells stably expressing human muscarinic receptor subtypes (M1-M5) are incubated with radiolabeled antagonist (e.g., [3H]-N-methylscopolamine) and varying concentrations of (+)-Cevimeline. After incubation at 25-37degC for 60-90 minutes, bound ligand is separated by rapid filtration through GF/B filters. Radioactivity is counted to determine Ki values.
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| Cell Assay |
Immortalized human salivary gland cell lines (e.g., NS-SV-AC) or primary human salivary gland acinar cells are loaded with Fluo-4 AM calcium dye. Cells are stimulated with varying concentrations of (+)-Cevimeline (1 nM to 100 uM), and intracellular calcium flux is measured as change in fluorescence (ex/em: 494/516 nm) over time. Salivary secretion is measured by accumulation of alpha-amylase in culture medium.
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| Animal Protocol |
Male Sprague-Dawley rats are anesthetized and the salivary ducts are cannulated. (+)-Cevimeline is administered intravenously (0.1-3 mg/kg) or orally (0.5-10 mg/kg). Saliva is collected from the cannulated ducts for 30-60 minutes and volume is measured gravimetrically. In unanesthetized animals, salivary secretion can be measured using pre-weighed cotton balls placed in the oral cavity.
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| ADME/Pharmacokinetics |
In humans, cevimeline (Evoxac®) is administered orally as 30 mg capsules three times daily. It is rapidly absorbed with Tmax approximately 1.5-2 hours. The terminal half-life is approximately 4-5 hours. It is primarily metabolized by CYP2D6 and CYP3A4 to active metabolites. Excretion occurs primarily via urine. Pharmacokinetics are linear within the therapeutic dose range.
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| Toxicity/Toxicokinetics |
The most common adverse effects are due to muscarinic overstimulation: excessive sweating (hyperhidrosis), nausea, rhinitis, diarrhea, and headache. Less common but more serious effects include bradycardia, hypotension, and visual disturbances (blurred vision). Contraindications include uncontrolled asthma, narrow-angle glaucoma, and acute iritis. Doses >90 mg three times daily are not recommended.
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| Additional Infomation |
(+)-Cevimeline hydrochloride (brand name Evoxac® in the US, Saligren® in Japan) is an FDA-approved and commercially available drug for the symptomatic treatment of xerostomia (dry mouth) in Sjögren's syndrome. It was first approved by the FDA in 2000. It represents the only oral muscarinic agonist specifically indicated for this condition.
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| Molecular Formula |
C10H17NOS.HCL.1/2H2O
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|---|---|
| Molecular Weight |
244.78
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| Related CAS # |
Cevimeline hydrochloride;107220-28-0;Cevimeline hydrochloride hemihydrate;153504-70-2;(-)-Cevimeline hydrochloride hemihydrate;Cevimeline;107233-08-9
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| Appearance |
Light yellow to yellow solid powder
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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) |
H2O :~100 mg/mL (~408.53 mM)
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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 | 4.0853 mL | 20.4265 mL | 40.8530 mL | |
| 5 mM | 0.8171 mL | 4.0853 mL | 8.1706 mL | |
| 10 mM | 0.4085 mL | 2.0427 mL | 4.0853 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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