MPTP (hydrochloride) [23007-85-4]

Cat# HY-15608-100mg

Size : 100mg

Brand : MedChemExpress

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Description

MPTP hydrochloride is a brain penetrant dopamine neurotoxin. MPTP hydrochloride can be used to induces Parkinson’s Disease model. MPTP hydrochloride, a precusor of MPP+, induces apoptosis[1][2][3]. MPTP hydrochloride has been verified by MCE with professional biological experiments.

In Vitro

Pretreatment with 50 mM 4-phenylpyridine, reduces IC50 (concentration for 50% inhibition of twitch amplitude) values of MPTP from 53 to 18 mM and d-tubocurarine from 0.7 to 0.3 mM, respectively, in mouse phrenic nerve-diaphragm[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

MPTP hydrochloride can be used in animal modeling to create Parkinson's disease models. MPTP replicates naturally occurring neurodegeneration and is useful for studying dopaminergic neuronal degeneration, mitochondrial dysfunction, and neuroinflammation. After injection, MPTP is rapidly metabolized to MPP+, which has a serum half-life of approximately 6 days in sheep.

Induction of Parkinsonism model[4][5][6][7]
Background
MPTP is free to cross the blood-brain barrier and enter the brain, where it is metabolized by monoamine oxidase B (MAO-B) in astrocytes into MPP+, its active & toxic form. MPP+ is taken up by dopamine neurons via a dopamine transporter (DAT), blocking Complex I in the electron transport chain of mitochondria, triggering oxidative stress and mitochondrial breakdown, and finally leading to neuron apoptosis. In Parkinson's disease, it is the loss of neurons in the substantia nigra, the dopamine-producing part of the substantia nigrostriatum system, that causes the disease. Due to the toxic effects of MPTP, it will cause the death of dopamine neurons in the substantia nigra, causing symptoms similar to Parkinson's disease.
Specific Modeling Methods
Mice: C57BL/6 • male • 8-12 week-old (period: 2 weeks), older mice may be more sensitive
Administration:
Acute model: 14-20 mg/kg • ip • 4 times in a day, two hours apart
Sub-acute model: 20-30 mg/kg • ip • once daily for 5 days
Note
1. MPTP Hcl is dissolved in normal saline and configured when used.
2. After administration, we can observe whether the mice have symptoms such as reduced activity, staggering walking, twitching, fried hair, increased urination, etc. This behavior may last for 24-48 hours, after which the mice behave basically normally.
3. MPTP is usually sold as MPTP hydrochloride. The molecular weight of MPTP hydrochloride is 209.7. Therefore, it is recommended to take into account the presence of hydrochloride (HCl) when preparing injectable solutions. HCl has a molecular weight of 35.4 and accounts for 17% of MPTP. Thus, if a 20 mg/kg dose of MPTP is to be prepared, the MPTP hydrochloride dose administered is 20 mg kg* 1.17% = 23.4 mg/kg.
4. If multiple injections are given within 1 day, it is best to alternate the injections on both sides. If injected every day, it should be done at the same time. Before each injection, the mice need to be weighed and the dosage volume should be adjusted.
5. Modeling mice may not show behavioral defects of Parkinson's disease. Mice may show individual differences, and the success rate of modeling is generally difficult to reach 100%. Therefore nigrostriatal damage associated with gliosis should be mainly monitored in MPTP mouse studies.
6. High drug dosage/mice weighing less than 22 g/mixing of drugs from different batches/mice not adapting in advance/animal room being too cold may result in a number of deaths. It is recommended that the number of animals in each group be increased, and adjust to the optimal dose according to experimental conditions.
Modeling Indicators
Nigrostriatal injury: Tyrosine hydroxylase in the substantia nigra and striatum is reduced after successful modeling (IHC, IF, WB, etc.);
Other markers: reduction of brain neurotransmitters (DA, DOPAC, 5-HT, HVA, etc.) (detected by HPLC);
Nigrostriatal microglia (IBA1+ cells) and astrocytes (GFAP+ cells) are activated, and the number of α-syn aggregates in the substantia nigra .
Correlated Product(s): /
Opposite Product(s): HY-W013494


Frequently Asked Question (FAQ):
1. Which mouse strain should be used and how old are they?
Currently, male C57bl/6 mice are commonly used in the references. Mice should be at least 8 weeks old, and 8-12 weeks mice are commonly used. The optimal weight is 25-30 g. Experimental reproducibility is better in mice above 8 weeks of age, and older mice may be more sensitive;
2. Which administration route should be used?
Although MPTP can be administered by a variety of different routes, including oral gavage and stereotaxic injection into the brain, the most common, and reproducible, results are obtained by systemic subcutaneous (s.c.) or intraperitoneal (i.p.) injection.
3. How should I choose the dosage?
The commonly used protocols in the references are acute model (20 mg/kg, i.p., given every 2 hours within a day, a total of 4 times) and subacute model (30 mg/kg, i.p., once daily for 5 days).
4. What phenotypes in mice can I observe?
Generally speaking, We can observe whether the mice have symptoms such as reduced activity, staggering walking, twitching, fried hair, increased urination, etc. This behavior may last for 24-48 hours, after which the mice behave basically normally.
5. What markers can be detected to indicate the success of modeling?
1) Nigrostriatal injury: Tyrosine hydroxylase in the substantia nigra and striatum is reduced after successful modeling (IHC, IF, WB, etc.);
2) Other markers: reduction of brain neurotransmitters (DA, DOPAC, 5-HT, HVA, etc.) (detected by HPLC);
3) Nigrostriatal microglia (IBA1+ cells) and astrocytes (GFAP+ cells) are activated, and the number of α-syn aggregates in the substantia nigra increases;

Note:
1. MPTP is usually sold as MPTP hydrochloride. The molecular weight of MPTP hydrochloride is 209.7. Therefore, it is recommended to take into account the presence of hydrochloride (HCl) when preparing injectable solutions. HCl has a molecular weight of 35.4 and accounts for 17% of MPTP.
Thus, if a 20 mg/kg dose of MPTP is to be prepared, the MPTP hydrochloride dose administered is 20 mg kg* 1.17% = 23.4 mg/kg.
2. If multiple injections are given within 1 day, it is best to alternate the injections on both sides. If injected every day, it should be done at the same time. Before each injection, the mice need to be weighed and the dosage volume should be adjusted.
3. Modeling mice may not show behavioral defects of Parkinson's disease. Mice may show individual differences, and the success rate of modeling is generally difficult to reach 100%. Therefore nigrostriatal damage associated with gliosis should be mainly monitored in MPTP mouse studies.
4. High drug dosage/mice weighing less than 22 g/mixing of drugs from different batches/mice not adapting in advance/animal room being too cold may result in a number of deaths, and it is recommended that the number of animals in each group be increased.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

209.72

Formula

C12H16ClN

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

CN1CC=C(C2=CC=CC=C2)CC1.06Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

H2O : ≥ 100 mg/mL (476.83 mM)

DMSO : 12 mg/mL (57.22 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 4.7683 mL 23.8413 mL 47.6826 mL
5 mM 0.9537 mL 4.7683 mL 9.5365 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 1.67 mg/mL (7.96 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 1.67 mg/mL (7.96 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  PBS

    Solubility: ≥ 100 mg/mL (476.83 mM); Clear solution

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).
Purity & Documentation
References

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