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MPTP hydrochloride

MCE China：MPTP hydrochloride

Brand：MedChemExpress (MCE)

Cat. No.HY-15608

CAS：23007-85-4

Purity：99.52%

Storage：4°C, sealed storage, away from moisture *In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)

Shipping：Room temperature in continental US; may vary elsewhere.

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. 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].

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. .f12{ font-size: 12px; } .fwb{ font-weight: bold; } .lh22{ line-height: 22px;; } .lh23 { line-height: 23px; } .pl13{ padding-left: 13px;; } .part { margin-top: 18px; } .mold-first-tit { width: 100%; height: 44px; line-height: 44px; background: #F9F7FB; border-bottom: 1px solid #EBE4F6; padding-left: 16px; box-sizing: border-box; margin-bottom: 17px; } .mold-second-tit:before { content:""; width: 6px; height: 6px; display: inline-block; border-radius: 50%; background: rgba(255,102,0,0.4); margin-right: 12px; position: relative; top: -3px; } .lft-border { border-left: 1px dotted #EBE4F6; padding-right: 12px; margin-left: 3px; box-sizing: border-box; padding-bottom: 12px; } /* .part .dec:last-child { border-bottom: 0; } */ .dec { margin: 10px 15px 0; padding-bottom: 10px; border-bottom: 1px dashed #EBE4F6; } .btm-border { border-left: 1px dashed #EBE4F6; } .text-bg { margin-top: 10px; background: #FFFBF1; padding: 14px; border-bottom: 0; position: relative; } .text-note-bg { margin-top: 10px; background: #FFFDF7; padding: 12px; border-bottom: 0; position: relative; } .text-note { width: 51px; height: 20px; line-height: 20px; background: #FFE2AA; text-align: center; border-radius: 0 0 8px 0; position: absolute; top: 0; left: 0; } .text-note-dec { margin-top: 15px;; } 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 Mmodeling 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 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

Animal Administration：For the preparation of the LPS rat model and the MPTP mouse model, the treatments of the animals are performed. Briefly, adult rats receive unilateral injections of LPS (0.5 μL of 10 μg/μL diluted in 0.9% saline) into the medial forebrain bundle (MFB) at the following coordinates, AP-4.2 mm, L 1.5 mm, and V 7.8 mm, and into the contralateral side with the same volume of 0.9% saline. Adult mice are administered intraperitoneal injections of MPTP of 25 mg/kg per day for five continuous days, and the same volume of saline is injected as a control. All the animals are sacrificed at week 1, 2, 3, or 4 after the LPS or MPTP injections. The brain samples are collected for the subsequent immunohistochemistry and western blot experiments.

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References：

[1]. Langston J W, Irwin I. MPTP Neurotoxicity: An Overview and Characterization of Phases of Toxicity. II. Selective Accumulation of MPP in the Substantia Nigra: A Key to Neurotoxicity (Question). Life Sci., 1985, 36, No. 3, 201-12.  [Content Brief]

[2]. Hsu K S, et al. Potentiation of MPTP by 4-Phenylpyridine on the Neuromuscular Blockade in Mouse Phrenic Nerve-Diaphragm. Neuropharmacology, 1993, 32, No. 9, 877-83.  [Content Brief]

[3]. Sun XL, et al. Gas1 up-regulation is inducible and contributes to cell apoptosis in reactive astrocytes in the substantia nigra of LPS and MPTP models. J Neuroinflammation. 2016 Jul 8;13(1):180.  [Content Brief]

[4]. Jackson-Lewis V, Przedborski S. Protocol for the MPTP mouse model of Parkinson's disease. Nat Protoc. 2007;2(1):141-51.  [Content Brief]

[5]. Rabaneda-Lombarte N, et al. The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson's disease. J Neuroinflammation. 2021 Apr 6;18(1):88.  [Content Brief]

[6]. Lee, et al. MPTP-driven NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration. Cell Death Differ. 2019 Jan;26(2):213-228.  [Content Brief]

[7]. Zhang QS, et al. Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease. Acta Pharmacol Sin. 2017 Oct;38(10):1317-1328.  [Content Brief]

[8]. Hammock BD, et al., A sheep model for MPTP induced Parkinson-like symptoms. Life Sci. 1989;45(17):1601-8.  [Content Brief]