| Identification | Back Directory | [Name]
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride | [CAS]
23007-85-4 | [Synonyms]
MPTP
MPTP HYDROCHLORIDE
NSC 139654 Hydrochloride
1-METHYL-4-PHENYL-1 2 3 6-TETRAHYDROPYR&
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinehydr
1-methyl-4-phenyl-1,2,3,6-tetra-*hydropyridine hy
1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine HCL
1,2,3,6-tetrahydro-1-methyl-4-phenylpyridinehydrochloride
1,2,3,6-tetrahydro-1-methyl-4-phenyl-pyridinhydrochloride
1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE HYDROCHLORIDE
N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE HYDROCHLORIDE
1- Methyl-4-phenyl -1,2,3,6-four hydrogen pyridinehydrochloride
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride, >=99%
Pyridine,1,2,3,6-tetrahydro-1-methyl-4-phenyl-, hydrochloride (1:1)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride,MPTP hydrochloride | [Molecular Formula]
C12H16ClN | [MDL Number]
MFCD00012790 | [MOL File]
23007-85-4.mol | [Molecular Weight]
209.72 |
| Chemical Properties | Back Directory | [Appearance]
White Solid | [Melting point ]
249.0 to 254.0 °C | [storage temp. ]
-20°C Freezer | [solubility ]
DMSO (Slightly), Methanol (Slightly), Water (Slightly) | [form ]
White solid | [color ]
white to off-white | [Water Solubility ]
water: 100mg/mL | [BRN ]
3707312 | [Stability:]
Light Sensitive | [InChI]
InChI=1S/C12H15N.ClH/c1-13-9-7-12(8-10-13)11-5-3-2-4-6-11;/h2-7H,8-10H2,1H3;1H | [InChIKey]
KOWJANGMTAZWDT-UHFFFAOYSA-N | [SMILES]
C1(=CCN(C)CC1)C1C=CC=CC=1.Cl | [CAS DataBase Reference]
23007-85-4 |
| Hazard Information | Back Directory | [Chemical Properties]
White Solid | [Uses]
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride is a dopaminergic neurotoxin that reportedly causes a severe and irreversible Parkinsonian condition in humans and monkeys. | [Uses]
MPTP is a neurotoxin used to cause selective destruction of dopaminergic neurons in animal models of parkinsonism. MPTP is metabolized by monoamine oxidase B to produce MPDP+ and MPP+, with MP+ being the active toxic agent. MPP+ induces neurotoxicity primarily by inhibiting complex I of the mitochondrial electron transport chain, resulting in ATP depletion and increased oxidative stress. The key features of different neurotoxic models of Parkinson’s disease, including the MPTP model, have been detailed.[Cayman Chemical] | [Biochem/physiol Actions]
Dopaminergic neurotoxin. | [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 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 | [storage]
Store at -20°C | [Purification Methods]
Purify MPTP by recrystallisation from pKEst ~ Me2CO/isoPrOH. The free base has m 40-42o(from heptane), b 99-100o/1.3mm, 128-132o/12mm, (137-142o/0.8mm), n 25 1.5347. The hydrochloride has m 251-252o(from Me2CO/isoPrOH) [Schmidle & Mansfield J Am Chem Soc 78 425 1956, Defeudis Drug Dev Res 15 1 1988, Beilstein 20 III/IV 3240, 20/7 V 121.] | [References]
[1] Lun-Yi Zang, Hara P Misra. “Inactivation of acetylcholinesterase by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride.” Molecular and Cellular Biochemistry 254 1–2 (2003): 131–6.
[2] Gregory L. Willis, Alan D. Robertson. “Recovery from experimental Parkinson’s disease in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride treated marmoset with the melatonin analogue ML-23.” Pharmacology Biochemistry and Behavior 80 1 (2005): Pages 9-26.
[3] Atsushi Fujita. “Connexin 30 deficiency attenuates A2 astrocyte responses and induces severe neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride Parkinson’s disease animal model.” Journal of Neuroinflammation (2018): 227.
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