| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
The unlabeled 3-O-Methyldopa is the major metabolite of the Parkinson‘s drug L-DOPA, formed by catechol-O-methyltransferase (COMT). It competitively inhibits the pharmacodynamics of L-DOPA and dopamine, potentially reducing the clinical effectiveness of L-DOPA therapy. The deuterated form is not a pharmacological tool but an analytical reference.
|
|---|---|
| ln Vitro |
3-O-Methyldopa (unlabeled) competitively inhibits L-DOPA and dopamine pharmacodynamics. In vitro, it blocks striatal uptake and utilization of L-DOPA. It also inhibits astrocyte-mediated dopaminergic neuroprotective effects of L-DOPA by competing with L-DOPA for action on target molecules. The d3 analog is used solely as an internal standard.
|
| ln Vivo |
3-O-Methyldopa (unlabeled) has been shown in rats to inhibit striatal uptake and utilization of L-DOPA, leading to significantly lower accumulation of L-DOPA, dopamine, and its metabolites compared to controls. In patients, it may reduce the clinical effectiveness of L-DOPA and contribute to the 'wearing-off‘ phenomenon.
|
| Enzyme Assay |
3-O-Methyldopa-d3 is not used in binding assays as a test compound. It is used as an internal standard in liquid chromatography-mass spectrometry (LC-MS) assays. A biological sample (plasma, urine, tissue) is spiked with a known amount of the deuterated standard, processed by protein precipitation or solid-phase extraction, and analyzed by LC-MS/MS.
|
| Cell Assay |
Cell-based experiments are not performed with the deuterated standard. To study the effects of the unlabeled metabolite, primary rat striatal neurons or astrocytes are treated with 3-O-Methyldopa, then challenged with L-DOPA. Neuroprotective readouts such as cell viability, dopamine uptake, or glutathione levels are measured to assess competition.
|
| Animal Protocol |
The unlabeled 3-O-Methyldopa is studied in vivo by administering it to rats prior to L-DOPA injection. 3-OMD is given intraperitoneally, followed by L-DOPA. Animals are then sacrificed, and striatal tissue is analyzed for L-DOPA, dopamine, and metabolite levels by HPLC-ECD to assess inhibition of L-DOPA utilization.
|
| ADME/Pharmacokinetics |
3-O-Methyldopa has a long plasma half-life (approximately 15 hours), significantly longer than L-DOPA's 1-hour half-life. This leads to its accumulation during chronic L-DOPA therapy in Parkinson‘s disease patients. The d3 standard is used to accurately quantify these levels and is chemically identical in behavior to the analyte.
|
| Toxicity/Toxicokinetics |
Toxicity Summary
Methoxytyrosine is one of the main biochemical markers of aromatic L-amino acid decarboxylase deficiency, a congenital metabolic defect that affects the biosynthesis of serotonin and dopamine. Elevated levels of 3-methoxytyrosine are found in cerebrospinal fluid, plasma, and urine. Catechol-O-methyltransferase, the enzyme responsible for the production of 3-methoxytyrosine, is derived from levodopa in many organs. However, its half-life (approximately 15 hours) is longer than that of levodopa (approximately 1 hour). This means it accumulates in the plasma and brain of patients receiving long-term levodopa treatment (e.g., those with Parkinson's disease). 3-Methoxytyrosine has some effect on levodopa-related motor dysfunction, including inhibiting striatal tyrosine uptake, competing with levodopa for transport along the blood-brain barrier, and inhibiting dopamine release. 3-Methoxytyrosine increases homocysteine levels, and this amino acid can induce cardiovascular disease and neuronal damage. Other toxic effects may include oxidative DNA damage (which can lead to cell death), decreased motility, and reduced mitochondrial membrane potential. (Wikipedia) No direct toxicological data is provided for the d3 internal standard, as it is used in minute amounts in analytical assays. The unlabeled 3-O-Methyldopa is not toxic per se, but its accumulation during L-DOPA therapy is associated with reduced therapeutic efficacy and may be involved in the 'wearing-off‘ phenomenon. |
| References | |
| Additional Infomation |
3-Methoxytyrosine is a derivative of tyrosine. It is one of the main biochemical markers of aromatic L-amino acid decarboxylase deficiency (AADC, EC 4.1.1.28), a congenital metabolic defect that affects the biosynthesis of serotonin and dopamine. Patients are usually diagnosed in infancy due to developmental delays, hypotonia, and extrapyramidal motor dysfunction. Diagnosis is based on abnormal neurotransmitter metabolite profiles in cerebrospinal fluid and decreased AADC activity in plasma. Elevated levels of 3-methoxytyrosine are found in cerebrospinal fluid, plasma, and urine. (A3381, A3382, A3383)
3-O-Methyldopa-d3 is a Critical and essential tool in clinical chemistry and pharmaceutical analysis. Its primary application is as an internal standard for GC-MS or LC-MS quantification of L-DOPA metabolism in plasma and cerebrospinal fluid, enabling the precise measurement needed to study the pharmacokinetics of L-DOPA and to assess the effects of COMT inhibitors on its metabolism. |
| Molecular Formula |
C10H10D3NO4
|
|---|---|
| Molecular Weight |
214.23
|
| Exact Mass |
214.103
|
| CAS # |
586954-09-8
|
| Related CAS # |
3-O-Methyldopa;300-48-1;(rac)-3-O-Methyl DOPA-d3;1219173-95-1;3-O-Methyldopa-d3 hydrate
|
| PubChem CID |
1670
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
1.055
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
15
|
| Complexity |
222
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
[2H]C([2H])([2H])OC1=C(C=CC(=C1)C[C@H](C(=O)O)N)O
|
| InChi Key |
PFDUUKDQEHURQC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C10H13NO4/c1-15-9-5-6(2-3-8(9)12)4-7(11)10(13)14/h2-3,5,7,12H,4,11H2,1H3,(H,13,14)
|
| Chemical Name |
2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoic acid
|
| 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 |
| 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 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 | 4.6679 mL | 23.3394 mL | 46.6788 mL | |
| 5 mM | 0.9336 mL | 4.6679 mL | 9.3358 mL | |
| 10 mM | 0.4668 mL | 2.3339 mL | 4.6679 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
