| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
5-HT2A, 5-HT2C, 5-HT3, and Histamine H1 Receptors; alpha2-Adrenergic Receptors. Mirtazapine D3 acts as a potent antagonist at presynaptic alpha2-adrenergic autoreceptors and heteroreceptors, leading to increased release of norepinephrine and serotonin. It also directly blocks 5-HT2, 5-HT3, and H1 receptors. This unique mechanism enhances noradrenergic and serotonergic transmission without the sexual dysfunction associated with SSRIs.
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| ln Vitro |
Mirtazapine exhibits high affinity for human histamine H1 receptors (Ki = 0.1-0.5 nM), 5-HT2A receptors (Ki = 1.6 nM), 5-HT2C receptors (Ki = 3.8 nM), 5-HT3 receptors (Ki = 3.5 nM), and alpha2-adrenergic receptors (Ki = 20-70 nM). It has low affinity for 5-HT1A, dopamine D1/D2, and muscarinic receptors, explaining its favorable side effect profile.
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| ln Vivo |
The phenotypic scores of MeCP2-null mice were improved by mirtazapine (ip; 10–50 mg/Kg; 14 days) treatment, which also normalized heart rate, respiratory rate, anxiety levels, and eliminated the jumping behavior [ 2].
In rat models, mirtazapine (10-30 mg/kg i.p.) increases extracellular levels of norepinephrine and dopamine in the prefrontal cortex and hippocampus by 100-200% as measured by microdialysis. It also normalizes heart rate, respiration rate, anxiety levels, and eliminates stereotypic hopping behavior in MeCP2-null mice (a model of Rett syndrome), leading to improved phenotypic scores. |
| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from CHO or HEK-293 cells expressing human 5-HT2A, 5-HT2C, 5-HT3, H1, or alpha2 adrenergic receptors. Membranes (10-50 microg protein) are incubated with appropriate radioligands ([3H]ketanserin for 5-HT2A, [3H]mesulergine for 5-HT2C, [3H]GR65630 for 5-HT3, [3H]pyrilamine for H1, [3H]rauwolscine for alpha2) and varying concentrations of mirtazapine D3 for 60 minutes at 25degC. Nonspecific binding is determined with excess cold ligand. Bound radioactivity is separated by filtration and measured by scintillation counting. Ki values are calculated using the Cheng-Prusoff equation.
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| Cell Assay |
To assess functional antagonism at 5-HT2A receptors, CHO cells expressing human 5-HT2A receptors are seeded in 96-well plates (50,000 cells/well) and loaded with the calcium-sensitive dye Fluo-4 AM (5 microM) for 60 minutes at 37degC. Cells are pre-incubated with varying concentrations of mirtazapine D3 for 30 minutes, then stimulated with 10 nM 5-HT, and intracellular calcium increases are measured by fluorescence (excitation 494 nm, emission 516 nm). IC50 values for inhibition of 5-HT-induced calcium flux are calculated.
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| Animal Protocol |
Animal/Disease Models: MeCP2-deficient mice [2]
Doses: 10-50 mg/Kg Route of Administration: intraperitoneal (ip) injection; 10-50 mg/kg; 14 days Experimental Results: The thickness of the somatosensory cortex of MeCP2-deficient mice was restored, especially II -Layer III and VI. Male Sprague-Dawley rats (250-350 g) undergo stereotaxic surgery for implantation of a microdialysis probe into the medial prefrontal cortex (AP +3.2 mm, ML +/-0.6 mm, DV -5.0 mm from bregma). After 24-48 hours recovery, aCSF is perfused at 1.5 microL/min, and dialysate samples are collected every 20 minutes. After baseline stabilization, mirtazapine D3 (3-30 mg/kg i.p.) or vehicle is administered. Norepinephrine, dopamine, and serotonin levels are quantified by HPLC-ECD with a limit of detection of ~0.5 nM. Changes in neurotransmitter levels are expressed as percent of baseline. |
| ADME/Pharmacokinetics |
Mirtazapine D3 serves as an internal standard for LC-MS/MS bioanalysis of mirtazapine. The parent drug mirtazapine is well absorbed orally (bioavailability ~50%), with a half-life of 20-40 hours, supporting once-daily dosing. It is highly protein bound (~85%), primarily to albumin and alpha1-acid glycoprotein. Mirtazapine is extensively metabolized by CYP3A4, CYP2D6, and CYP1A2, and is excreted in urine (75%) and feces (15%).
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| Toxicity/Toxicokinetics |
Mirtazapine is generally well tolerated with a safety profile distinct from SSRIs. The most common side effects include sedation/somnolence (54% at high doses), increased appetite (17%), weight gain (12-15%), dry mouth (25%), and constipation. Unlike SSRIs, it has minimal sexual dysfunction or gastrointestinal side effects. Rare but serious side effects include agranulocytosis (0.1%), seizures, and serotonin syndrome.
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| References |
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| Additional Infomation |
Mirtazapine (Remeron®) was FDA-approved in 1996 for the treatment of major depressive disorder. The D3-labeled version is a research internal standard used in clinical pharmacology, forensic toxicology, and therapeutic drug monitoring for precise quantification of mirtazapine in biological samples. It is also used in drug-drug interaction studies and LC-MS method development.
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| Molecular Formula |
C₁₇H₁₆D₃N₃
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|---|---|
| Molecular Weight |
268.37
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| Exact Mass |
268.177
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| CAS # |
1216678-68-0
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| Related CAS # |
Mirtazapine;85650-52-8;(S)-Mirtazapine;61337-87-9;(S)-Mirtazapine-d3;(R)-Mirtazapine;61364-37-2;(R)-Mirtazapine-d3
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| PubChem CID |
45039945
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| Appearance |
White to off-white solid powder
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| LogP |
2.481
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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
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| Heavy Atom Count |
20
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| Complexity |
345
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])N1CCN2C(C1)C3=CC=CC=C3CC4=C2N=CC=C4
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| InChi Key |
RONZAEMNMFQXRA-FIBGUPNXSA-N
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| InChi Code |
InChI=1S/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3/i1D3
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| Chemical Name |
5-(trideuteriomethyl)-2,5,19-triazatetracyclo[13.4.0.02,7.08,13]nonadeca-1(15),8,10,12,16,18-hexaene
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| Synonyms |
Org 3770 D3 Org3770 D3 Mirtazapine D3 6-Azamianserin D3Org-3770 D3
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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) |
DMSO : ~100 mg/mL (~372.62 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.32 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 (9.32 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 (9.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7262 mL | 18.6310 mL | 37.2620 mL | |
| 5 mM | 0.7452 mL | 3.7262 mL | 7.4524 mL | |
| 10 mM | 0.3726 mL | 1.8631 mL | 3.7262 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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