| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary targets of Amitriptyline-d3 hydrochloride are the serotonin reuptake transporter (SERT) and the noradrenaline reuptake transporter (NET). It exhibits Ki values of 3.45 nM and 13.3 nM for human SERT and NET, respectively. It also shows weak binding to the dopamine reuptake transporter (DAT) with a Ki of 2.58 μM. Additionally, it interacts with various receptors, including serotonin 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7, noradrenaline α1, histamine H1, acetylcholine muscarinic receptors, and opiate σ1 receptors. It also acts as an agonist for TrkA and TrkB receptors.
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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].
The compound functions by inhibiting the reuptake of serotonin and noradrenaline at the presynaptic neuronal membrane. This inhibition leads to an increased concentration of these neurotransmitters in the synaptic cleft, thereby enhancing neurotransmission. The elevation of extracellular biogenic amine levels is the primary mechanism underlying its antidepressant effects. As a TrkA and TrkB receptor agonist, it also exhibits neurotrophic activity. In vitro studies typically involve assessing its binding affinity to transporters and receptors using radioligand binding assays. |
| ln Vivo |
In vivo, Amitriptyline-d3 hydrochloride is used as a tracer to study the pharmacokinetics and metabolic pathways of amitriptyline. The deuterium atoms allow for precise quantification of the drug and its metabolites in biological systems. Its pharmacological profile is identical to that of amitriptyline, which is known for its antidepressant activity. Animal model studies have demonstrated its efficacy in models of depression, where it increases the synaptic concentration of serotonin and noradrenaline, leading to mood enhancement. The compound is also used in neuroprotection research due to its Trk receptor agonist activity.
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| Enzyme Assay |
Typical cell-free assays involve radioligand binding studies to determine the compound's affinity (Ki) for SERT, NET, and DAT using membrane preparations from cells expressing these transporters. Competition binding experiments are performed with tritiated ligands, and the Ki values are calculated from IC50 values using the Cheng-Prusoff equation. For receptor binding studies, similar assays are conducted using membrane preparations from cells expressing various serotonin, adrenergic, histamine, and muscarinic receptors. The compound's agonist activity at TrkA and TrkB receptors is typically assessed using phosphorylation assays in cell-free systems.
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| Cell Assay |
In vitro cellular assays are conducted to evaluate the compound's effects on neurotransmitter uptake. Cells expressing human SERT or NET are incubated with the compound and a radiolabeled substrate (e.g., ³H-serotonin or ³H-noradrenaline), and the inhibition of uptake is measured. The IC50 values are then determined to assess potency. Additionally, cell-based assays are used to study the compound's neurotrophic activity, where cells expressing TrkA or TrkB receptors are treated with the compound, and receptor phosphorylation is measured to confirm agonist activity. These assays help elucidate the compound's mechanism of action at the cellular level.
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| Animal Protocol |
In vivo animal experiments typically involve administering the compound to rodents (e.g., rats or mice) via oral gavage or injection. Blood samples are collected at various time points to measure plasma concentrations of the deuterated compound and its metabolites using LC-MS/MS. The compound's antidepressant-like effects are evaluated using behavioral models such as the forced swim test or tail suspension test. For neurotrophic studies, the compound's ability to promote neuronal survival or regeneration is assessed in animal models of nerve injury or neurodegeneration.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Amitriptyline-d3 hydrochloride mirror those of amitriptyline. It is absorbed from the gastrointestinal tract, with highly variable peak plasma concentrations occurring between 2 and 12 hours after oral administration. The bioavailability of the active drug is between 30% and 60% due to extensive first-pass metabolism in the liver, primarily by CYP2D6. It is metabolized mainly via CYP2C19 and CYP2D6 pathways. Metabolism by CYP2C19 results in active metabolites, including nortriptyline. The elimination half-life varies from 10 to 50 hours, with an average of 15 hours. Within 24 hours, approximately 25-50% of a dose is excreted in the urine as inactive metabolites.
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| Toxicity/Toxicokinetics |
The toxicity profile of Amitriptyline-d3 hydrochloride is expected to be similar to that of amitriptyline. Common adverse effects associated with amitriptyline include drowsiness, dry mouth, blurred vision, constipation, and weight gain, which are attributed to its antagonism of histamine H1, muscarinic, and adrenergic receptors. In overdose, it can cause serious cardiotoxicity, including arrhythmias and conduction disturbances. The deuterium labeling does not alter the toxicity profile, as the pharmacological activity remains unchanged. Toxicological studies typically involve acute and chronic dosing in animal models to assess safety margins and identify potential target organ toxicities.
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| References |
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| Additional Infomation |
Amitriptyline, the parent compound, is a well-established tricyclic antidepressant marketed under brand names such as Elavil, Tryptizol, and Laroxyl for the treatment of major depression, clinical/endogenous depression, and involutional melancholia. The deuterated form (Amitriptyline-d3 hydrochloride) is not a therapeutic agent but serves as an analytical standard for research purposes. Its role in drug development is primarily as a tracer for quantitation during the drug development process, leveraging the impact of deuterium substitution on pharmacokinetic and metabolic profiles. It is also used in forensic and clinical toxicology analysis.
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| Molecular Formula |
C20H21D3CLN
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|---|---|
| Molecular Weight |
316.88
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| Exact Mass |
316.178
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| CAS # |
342611-00-1
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| Related CAS # |
Amitriptyline hydrochloride;549-18-8
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| PubChem CID |
46780369
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| Appearance |
White to off-white solid powder
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| Melting Point |
196-197ºC
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| Flash Point |
9℃
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| LogP |
4.97
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
331
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])N(C)CCC=C1C2=CC=CC=C2CCC3=CC=CC=C31.Cl
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| InChi Key |
KFYRPLNVJVHZGT-NIIDSAIPSA-N
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| InChi Code |
InChI=1S/C20H23N.ClH/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20;/h3-6,8-12H,7,13-15H2,1-2H3;1H/i1D3;
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| Chemical Name |
N-methyl-3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenylidene)-N-(trideuteriomethyl)propan-1-amine;hydrochloride
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | 3.1558 mL | 15.7788 mL | 31.5577 mL | |
| 5 mM | 0.6312 mL | 3.1558 mL | 6.3115 mL | |
| 10 mM | 0.3156 mL | 1.5779 mL | 3.1558 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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