MPTP

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Structural formula
Structure of MPTP
General
Surname MPTP
other names

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Molecular formula C 12 H 15 N
External identifiers / databases
CAS number 28289-54-5
EC number 248-939-7
ECHA InfoCard 100,044,475
PubChem 1388
Wikidata Q239816
properties
Molar mass 173.25 g mol −1
Physical state

firmly

Melting point

40 ° C

solubility

slightly soluble in water (2.93 g l −1 at 25 ° C)

safety instructions
GHS labeling of hazardous substances
08 - Dangerous to health 06 - Toxic or very toxic

danger

H and P phrases H: 301-370
P: 260-301 + 310-307 + 311
Toxicological data

86 mg kg −1 ( LD 50mouse , unknown )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

MPTP ( 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ) is a neurotoxin that triggers the symptoms of Parkinson's disease . As a precursor of the inhibitor of the mitochondrial respiratory chain MPP + (1-methyl-4-phenyl-pyridine), MPTP leads to the destruction of dopaminergic cells in the human brain (in the substantia nigra ) and is therefore also known as nigrostriatal toxin .

MPTP arises from the improper manufacture of MPPP (1-methyl-4-phenyl-4-propion-oxy-piperidine). MPPP is a designer drug and is also called synthetic heroin . The synthesis of MPPP must take place slowly and with little heat input. However, if a large amount of heat is applied briefly, this synthesis produces a large amount of MPTP.

Within a week, the patients injected with a mixture of MPPP and MPTP had a sudden twitch of the extremities followed by bradykinesia . These patients had symptoms similar to Parkinson's disease (such as difficulty moving and speaking, bent posture, increased salivation ( hypersalivation ), increased muscle activity, and the cogwheel phenomenon ( rigidity ) in the upper extremities). In contrast to patients whose Parkinson's disease had developed for no apparent cause, these patients were young, not demented and had an acute onset of Parkinson's disease . The postural tremor of the hull Windwärts located extremities was more pronounced than the typical resting tremor .

In later studies it was found that MPTP is converted into a positively charged compound MPP + ( 1-methyl-4-phenylpyridinium ) by an endogenous enzyme , MAO-B ( monoamine oxidase -B) . MPP + is then introduced into dopaminergic cells via an active transport mechanism through the dopamine transporter (DAT). In these cells, MPP + leads to an irreversible inhibition of mitochondrial complex I of the respiratory chain and thus leads to programmed cell death ( apoptosis ) of these nerve cells.

Today, MPTP is partly used in research to study Parkinson's disease in animal experiments .

Individual evidence

  1. a b c Entry on MPTP in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  2. a b Data sheet 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine from Sigma-Aldrich , accessed on May 5, 2011 ( PDF ).
  3. Burns, RS et al. (1983): A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In: Proc. Natl. Acad. Sci. USA 80 (14): 4546-4550. PMID 6192438 , PMC 384076 (free full text).
  4. Salach, JI et al. (1984): Oxidation of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidases A and B and suicide inactivation of the enzymes by MPTP. In: Biochem. Biophys. Res. Commun. 125 (2): 831-835. PMID 6335034
  5. Singer, TP et al. (1986): Interactions of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidases. In: Biochem. J. 235 (3): 785-789. PMID 3489461 , PMC 1146756 (free full text).
  6. Javitch JA, (1985): Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. In: Proc. Natl. Acad. Sci. USA 82 (7): 2173-2177. PMID 3872460 , PMC 397515 (free full text).
  7. Nicklas, WJ et al. (1985): Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. In: Life Sci. 36 (26): 2503-2508. PMID 2861548
  8. Schapira, AH et al. (1990): Mitochondrial complex I deficiency in Parkinson's disease. In: J. Neurochem. 54 (3): 823-827. PMID 2154550
  9. Cleeter MW (1992): Irreversible inhibition of mitochondrial complex I by 1-methyl-4-phenylpyridinium: evidence for free radical involvement. In: J. Neurochem. 58 (2): 786-789. PMID 1729421
  10. Przedborski, S. et al. (2001): The parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a technical review of its utility and safety. In: J. Neurochem. 76 (5): 1265-1274. PMID 11238711

literature

  • Lessel, Jürgen (1994): MPTP - Neurotoxin and Model Substance in Parkinson's Research. In: Pharmacy in our time . 23 (2): 106-107. doi : 10.1002 / pauz.19940230211
  • JW Langston, J. Palfreman: The case of the frozen addicts , Amsterdam, IOS Press 2014

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