| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
Muscarinic acetylcholine receptors (mAChR), specifically M1 and M3 subtypes. These G protein-coupled receptors mediate exocrine gland secretion. The (-)-enantiomer of cevimeline is expected to have significantly lower binding affinity for these receptors. It may be used in research as a negative control to verify stereospecificity of muscarinic agonist effects.
|
|---|---|
| ln Vitro |
While (+)-Cevimeline is a potent muscarinic agonist with Ki values in the low nanomolar range, (-)-Cevimeline shows reduced activity in functional assays. Its ability to increase intracellular calcium and stimulate amylase secretion from salivary gland cells is substantially diminished. This makes it useful as a control to demonstrate that observed biological activity is stereospecific.
|
| ln Vivo |
In animal models of salivary secretion (e.g., anesthetized rats with cannulated salivary ducts), (-)-Cevimeline produces significantly less salivary flow compared to the (+)-enantiomer at equivalent doses. At high doses, any residual sialagogue effect can be fully blocked by the muscarinic antagonist atropine, confirming its mechanism, but with much lower potency.
|
| Enzyme Assay |
Competitive radioligand binding assays using membranes from CHO cells expressing human M1 or M3 receptors are performed. Membranes are incubated with [3H]-N-methylscopolamine or [3H]-QNB (quinuclidinyl benzilate) and varying concentrations of (-)-Cevimeline (0.1 nM to 100 uM). After filtration, radioactivity is counted. The Ki of (-)-Cevimeline is compared to the active (+)-enantiomer. At least 10-100 fold reduction in binding affinity is expected.
|
| Cell Assay |
Human salivary gland (NS-SV-AC) cells are loaded with Fluo-4 AM calcium dye. Cells are stimulated with (-)-Cevimeline (1 nM - 100 uM), and intracellular calcium flux is measured. The EC50 for the (-)-enantiomer is expected to be significantly higher (i.e., less potent) than for (+)-Cevimeline. Amylase secretion from parotid acinar cells is measured by enzymatic assay.
|
| Animal Protocol |
Male Sprague-Dawley rats are anesthetized, and the submandibular ducts are cannulated. (-)-Cevimeline (0.1-10 mg/kg) is administered intravenously or orally. Saliva is collected and volume measured. In studies using the (+)- and (-)-enantiomers, a clear rightward shift in the dose-response curve is observed for the (-)-enantiomer, demonstrating stereospecificity of the drug-receptor interaction.
|
| ADME/Pharmacokinetics |
Pharmacokinetic parameters for (-)-Cevimeline are expected to be similar to the (+)-enantiomer (oral absorption, Tmax 1.5-2 hours, half-life 4-5 hours) due to identical physicochemical properties. However, its pharmacodynamic effect (salivary flow) will be significantly lower at equivalent plasma concentrations, confirming that the therapeutic effect of racemic cevimeline is primarily due to the (+)-enantiomer.
|
| Toxicity/Toxicokinetics |
The toxicity profile of (-)-Cevimeline is expected to be similar to that of the racemate or (+)-enantiomer at high doses, including excessive muscarinic effects: sweating, nausea, diarrhea, bradycardia, and blurred vision. However, because it is less potent, the risk of these effects at equimolar doses is lower. The compound is not used clinically as a single enantiomer.
|
| Additional Infomation |
The clinical drug product Evoxac® (cevimeline hydrochloride) is a racemic mixture of (+)- and (-)-enantiomers. Cevimeline is approved by the FDA and other global regulatory agencies for the treatment of xerostomia in Sjögren's syndrome. The (-)-enantiomer is a research compound used to study the stereochemistry of muscarinic receptor activation. It is not separately approved for clinical use.
|
| Molecular Formula |
C10H17NOS.HCL.1/2H2O
|
|---|---|
| Molecular Weight |
244.78
|
| Related CAS # |
Cevimeline hydrochloride hemihydrate;153504-70-2;(+)-Cevimeline hydrochloride hemihydrate
|
| Appearance |
Light yellow to yellow solid powder
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
H2O :~100 mg/mL (~408.53 mM)
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
