| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Target: Mitochondrial Complex I (NADH:ubiquinone oxidoreductase). MPP+ is taken up into dopaminergic neurons via the dopamine transporter (DAT). Once inside, it accumulates in mitochondria and inhibits Complex I of the mitochondrial electron transport chain, leading to ATP depletion, oxidative stress (ROS production), and ultimately selective death of dopaminergic neurons in the substantia nigra pars compacta. The labeled version is an analytical standard.
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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].
In vitro, the labeled standard has no direct biological activity. The unlabeled MPP+ iodide (0.1-100 uM) causes concentration- and time-dependent death of dopaminergic cell lines (e.g., SH-SY5Y, PC12, MN9D) and primary mesencephalic dopaminergic neurons. It decreases mitochondrial membrane potential (deltaΨm), increases reactive oxygen species (ROS), and induces caspase-dependent and caspase-independent apoptosis. MPP+ also inhibits tyrosine hydroxylase (TH) expression and dopamine synthesis. |
| ln Vivo |
In vivo, MPP+ iodide (1-10 ug, stereotaxic injection into the striatum or substantia nigra) is used to induce Parkinson's disease (PD) in rodent and non-human primate models. It causes selective loss of dopaminergic neurons in the substantia nigra pars compacta, depletion of striatal dopamine, and motor deficits (bradykinesia, rigidity, postural instability). MPP+ is considered the active toxic species responsible for MPTP-induced parkinsonism. The deuterated standard is not administered in vivo for efficacy studies; it is used as an internal standard for quantification in PK studies.
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| Enzyme Assay |
For cell-free assays: mitochondrial fractions isolated from brain tissue or cell lines are incubated with varying concentrations of MPP+ (0-1000 uM) and NADH in assay buffer. Complex I activity is measured spectrophotometrically by the rate of NADH oxidation (decrease in absorbance at 340 nm) or by measuring the reduction of ubiquinone analogs (e.g., decylubiquinone). IC50 values for Complex I inhibition are determined. The deuterated standard is not used in these assays; it is used for LC-MS quantification of MPP+ in samples.
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| Cell Assay |
For cell-based assays: dopaminergic SH-SY5Y cells are seeded in 96-well plates and treated with MPP+ iodide (0.1-1000 uM, 24-72 h). Cell viability is measured by MTT, CCK-8, or LDH release assay. Mitochondrial membrane potential (deltaΨm) is measured by JC-1 or TMRM staining by flow cytometry or fluorescence microscopy. ROS production is measured by DCFH-DA fluorescence. Apoptosis is assessed by Annexin V/PI flow cytometry or by caspase-3/7 activity assays. The deuterated standard is not used in these assays but is used for LC-MS quantification of MPP+ uptake in the cells.
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| Animal Protocol |
For in vivo animal studies: mice or rats are administered MPTP (20-40 mg/kg, IP, multiple doses) or MPP+ is directly injected into the striatum or substantia nigra (unilateral stereotaxic injection, 1-10 ug). After 7-21 days, animals are euthanized, and striatal tissue is dissected for dopamine and metabolite (DOPAC, HVA) analysis by HPLC-ECD. Nigral tissue is processed for tyrosine hydroxylase (TH) immunohistochemistry to count remaining dopaminergic neurons. For PK studies, animals are administered MPP+ (IV or IP), and blood or brain tissue samples are analyzed using MPP+-d3 iodide internal standard by LC-MS/MS to determine concentrations, distribution, and elimination of MPP+. The labeled standard is used in bioanalysis but is not administered to animals directly.
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| ADME/Pharmacokinetics |
PK properties of MPP+: after MPTP administration, MPP+ is rapidly formed in the brain and accumulates in dopaminergic neurons via DAT. The half-life of MPP+ in the brain is approximately 2-4 h in mice. It is slowly cleared from the substantia nigra and striatum over several days. The deuterated standard co-elutes with the unlabeled MPP+ in LC-MS/MS, ensuring accurate quantification. PK parameters in plasma show rapid clearance (t1/2 ~1-2 h) with limited systemic exposure when MPP+ is administered directly (as opposed to MPTP). The labeled standard does not exhibit distinct PK behavior.
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| Toxicity/Toxicokinetics |
Toxicity profile of MPP+ (unlabeled): MPP+ is highly toxic to dopaminergic neurons and causes irreversible Parkinson‘s disease in animal models. In humans, MPTP (the prodrug) can cause severe, permanent parkinsonism similar to idiopathic PD. MPP+ is toxic to other cell types at high concentrations but has relative selectivity for dopaminergic neurons due to DAT-mediated uptake. The labeled compound is for research use only and is not intended for human administration. It is non-hazardous for transport under normal laboratory conditions, but MPP+ should be handled with appropriate safety precautions due to its neurotoxicity. The deuterated standard is non-toxic at the low concentrations used for analytical purposes.
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| References |
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| Additional Infomation |
MPP+-d3 iodide is a research standard and is not an approved drug. It is used as a chemical tool in Parkinson's disease research to induce PD-like pathology in animal models and cell-based assays. It is essential for studying the mechanisms of dopaminergic neurodegeneration, mitochondrial dysfunction, and oxidative stress in PD. The labeled standard is used as an internal standard for LC-MS/MS quantification of MPP+ in PK, tissue distribution, and metabolism studies of MPTP and related compounds. It is also used in quality control for research-grade chemicals and as a reference standard for MPTP/MPP+ analysis in forensic and toxicology studies.
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| Molecular Formula |
C12H9D3IN
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|---|---|
| Molecular Weight |
300.15300
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| Exact Mass |
300.02
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| CAS # |
207556-07-8
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| Related CAS # |
MPP+ iodide;36913-39-0
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| PubChem CID |
16212321
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| Appearance |
Off-white to light yellow solid powder
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| Melting Point |
168-169ºC(lit.)
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
14
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| Complexity |
141
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])[N+]1=CC=C(C=C1)C2=CC=CC=C2.[I-]
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| InChi Key |
RFDFRDXIIKROAI-NIIDSAIPSA-M
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| InChi Code |
InChI=1S/C12H12N.HI/c1-13-9-7-12(8-10-13)11-5-3-2-4-6-11;/h2-10H,1H3;1H/q+1;/p-1/i1D3;
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| Chemical Name |
4-phenyl-1-(trideuteriomethyl)pyridin-1-ium;iodide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | 3.3317 mL | 16.6583 mL | 33.3167 mL | |
| 5 mM | 0.6663 mL | 3.3317 mL | 6.6633 mL | |
| 10 mM | 0.3332 mL | 1.6658 mL | 3.3317 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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