| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Melatonin receptors MT1 and MT2. Agomelatine (the parent compound) is a specific agonist of MT1 and MT2 receptors with Ki values of 0.1 nM (CHO-hMT1), 0.06 nM (HEK-hMT1), 0.12 nM (CHO-hMT2), and 0.27 nM (HEK-hMT2). It is also a selective 5-HT2C receptor antagonist with pKi values of 6.4 at native (porcine) and 6.2 at cloned human 5-HT2C receptors. Agomelatin-d3 retains the same receptor binding profile.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
As a deuterated standard, Agomelatin-d3 is not typically used in functional activity assays but rather as an internal standard for quantitative analysis. The parent compound agomelatine acts as an MT1/MT2 agonist, leading to resynchronization of circadian rhythms, and as a 5-HT2C antagonist, enhancing frontocortical dopaminergic and noradrenergic pathways. The deuterium label does not alter the pharmacological activity but provides analytical advantages. |
| ln Vivo |
The parent compound agomelatine has demonstrated efficacy in preclinical models of depression and circadian rhythm disorders. Agomelatin-d3 itself is not used in in vivo efficacy studies because it is an isotopically labeled standard. The compound is employed in pharmacokinetic and metabolic studies to precisely quantify agomelatine levels in plasma, tissues, and excreta following administration of the non-deuterated drug.
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| Enzyme Assay |
For analytical method development, Agomelatin-d3 is used as an internal standard. Stock solutions are prepared in methanol or acetonitrile at 1 mg/mL concentration. Calibration curves are constructed by spiking blank biological matrix (plasma, urine, or tissue homogenate) with known concentrations of unlabeled agomelatine (0.1-1000 ng/mL) and a fixed concentration of Agomelatin-d3 (e.g., 50 ng/mL). Samples are processed by protein precipitation with acetonitrile or liquid-liquid extraction with methyl tert-butyl ether, followed by centrifugation. The supernatant is evaporated to dryness under nitrogen and reconstituted in mobile phase. Analysis is performed by LC-MS/MS using multiple reaction monitoring (MRM) mode, monitoring transitions for agomelatine and Agomelatin-d3 separately. The peak area ratio of analyte to internal standard is plotted against nominal concentration to generate a calibration curve.
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| Cell Assay |
For cellular assays, Agomelatin-d3 is not typically used because it is a stable isotope-labeled standard. However, in comparative studies, cells expressing MT1 or MT2 receptors (CHO or HEK293 cells) can be treated with agomelatine (0.01-1000 nM) to assess receptor activation via cAMP inhibition assays, with Agomelatin-d3 serving as an internal standard for LC-MS/MS quantification of drug concentrations in cell lysates or media. Cells are seeded in 6- or 96-well plates, treated with compound, and at specified time points, medium is collected and frozen at -80degC. After protein precipitation with acetonitrile containing Agomelatin-d3 (50 ng/mL), supernatants are analyzed by LC-MS/MS. Receptor functional activity (cAMP, calcium, or beta-arrestin recruitment) is measured separately by HTRF or luminescence assays.
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| Animal Protocol |
Agomelatin-d3 is not used in animal studies as a test agent, but rather as an analytical standard for pharmacokinetic studies of agomelatine. In such studies, animals (rats, mice, or dogs) receive oral or intravenous administration of agomelatine (1-30 mg/kg). Blood samples are collected at predetermined time points (0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose). Plasma is separated by centrifugation and stored at -80degC. For analysis, plasma samples (50-100 microL) are spiked with Agomelatin-d3 internal standard (20-100 ng/mL), proteins are precipitated with acetonitrile, and the supernatant is analyzed by LC-MS/MS. Pharmacokinetic parameters (Cmax, Tmax, AUC, half-life, clearance, volume of distribution, oral bioavailability) are calculated using non-compartmental analysis. Tissue distribution studies follow a similar protocol.
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| ADME/Pharmacokinetics |
Agomelatin-d3 (molecular weight 246.32 Da, formula C15H14D3NO2) has physicochemical properties identical to agomelatine except for the isotopic substitution. The deuterium label does not significantly alter absorption, distribution, or protein binding compared to the parent compound. Agomelatine itself has oral bioavailability of approximately 80% in rats and 35-50% in humans, a plasma half-life of 1-2 hours, high plasma protein binding (approximately 95%), and extensive hepatic metabolism primarily by CYP1A2 and CYP2C9. Agomelatin-d3 exhibits the same pharmacokinetic behavior when used as an internal standard, providing accurate quantification of agomelatine concentrations.
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| Toxicity/Toxicokinetics |
Agomelatin-d3 is chemically stable and non-toxic at the concentrations used as an internal standard (ng/mL levels). The parent compound agomelatine is generally well tolerated in clinical use with common adverse effects including headache, nasopharyngitis, and somnolence, and rare cases of hepatotoxicity have been reported. Agomelatin-d3 itself has not been subjected to formal toxicological evaluation as it is not administered as a therapeutic agent. Standard laboratory safety precautions for handling organic solvents and chemicals should be followed.
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| References |
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| Additional Infomation |
Agomelatin-d3 is a stable isotope-labeled internal standard for quantitative LC-MS/MS analysis of agomelatine in biological matrices. The three deuterium atoms are located on the acetamide group (acetamide-2,2,2-d3). Isotopic enrichment is typically ≥98% deuterium. The compound is particularly useful for pharmacokinetic studies, bioequivalence studies, and drug-drug interaction studies of agomelatine formulations. CAS number: 1079389-38-0. For research use only, not for human therapeutic administration.
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| Molecular Formula |
C15H14D3NO2
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|---|---|
| Molecular Weight |
246.32
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| Exact Mass |
246.144
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| CAS # |
1079389-38-0
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| Related CAS # |
Agomelatine;138112-76-2
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| PubChem CID |
25174581
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| Appearance |
White to off-white solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
18
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| Complexity |
280
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(C1=CC=CC2C=CC(OC)=CC1=2)CNC(=O)C([2H])([2H])[2H]
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| InChi Key |
YJYPHIXNFHFHND-FIBGUPNXSA-N
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| InChi Code |
InChI=1S/C15H17NO2/c1-11(17)16-9-8-13-5-3-4-12-6-7-14(18-2)10-15(12)13/h3-7,10H,8-9H2,1-2H3,(H,16,17)/i1D3
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| Chemical Name |
2,2,2-trideuterio-N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide
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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 | 4.0598 mL | 20.2988 mL | 40.5976 mL | |
| 5 mM | 0.8120 mL | 4.0598 mL | 8.1195 mL | |
| 10 mM | 0.4060 mL | 2.0299 mL | 4.0598 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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