Skip to main content

Relations between MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine), the Neurotoxin MPP+ (1-Methyl-4-Phenylpyridinium Ion), and MAO in Rat Brain

  • Chapter

Abstract

A fundamental biological characteristic of Parkinson’s disease is a damaged dopamine (DA) system between the substantia nigra and the corpus striata. This disease is a slowly progressive-neurodegenerative disorder pathologically characterized by the loss of neurons in the zona compacta of the substantia nigra. The etiology of this disease has been extensively investigated, but the precise reason for the loss of DA producing cells in this region remains obscure. Previous animal models of this disease were made by nigrostriatal lesion, depletion of DA with reserpine or α-methyl-p-tyrosine, blockage of the DA receptor with neuroleptics such as haloperidol, destruction of the substantia nigra with 6-hydroxy-DA (see review, Zigmond and Striker, 1984) or manganese intoxication (Donaldson et al., 1982).

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Castagnoli Jr. N., Chiba K., and Trevor A.J. (1985) Potential bioactivation pathways for the neurotoxin 1- methy 1-4-pheny 1-1,2,3,6-tetrahydropyridine (MPTP). Life Sci. 36 225–230.

    Article  PubMed  CAS  Google Scholar 

  • Chiba K., Trevor A., and Castagnoli Jr.N. (1984) Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem. Biophys. Res. Commun. 120 574–578.

    Article  PubMed  CAS  Google Scholar 

  • Del Zompo M., Pintus S., Zuddas A., and Corsini G.V. (1984) Deprenyl selectively inhibits [3H]MPTP binding sites in monkey brain. Eur. J. Pharmacol. 107 285–286.

    Article  Google Scholar 

  • Donaldson J., McGregor D., and LaBella F. (1982) Manganese neurotoxicity: A model for free radical mediated neurodegeneration? Can. J. Pharmacol. 107 1398–1405.

    Article  Google Scholar 

  • Fowler C.J., Magnusson O., and Ross S.B. (1984) Intra- and extra-neuronal monoamine oxidase. Blood vessel 21 126–131.

    CAS  Google Scholar 

  • Fuller R.W. and Steranka L.R. (1985) Central and peripheral catecholamine depletion by 1-methyl-4-phenyl-tetra- hydropyridine (MPTP) in rodents. Life Sci. 36 243–247.

    Article  PubMed  CAS  Google Scholar 

  • Hallman H., Olson L., and Jonsson G. (1984) Neurotoxicity of the meperidine analogue N-methyl-4-phenyl-1,2,3,6- tetrahydropyridine on brain catecholamine neurons in the mouse. Eur. J. Pharmacol. 97 133–136.

    Article  PubMed  CAS  Google Scholar 

  • Heikkila R.E., Hess A., and Duvoisin R.C.(1984) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine in mice. Science 244 1451–1453.

    Article  Google Scholar 

  • Heikkila R. E., Hess A., and Duvoisin R. C. (1985a) Dopaminergic neurotoxicity of 1-me thyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in mouse: Relationship between monoamine oxidase, MPTP metabolism and neurotoxicity. Life Sci. 36 231–236.

    Article  PubMed  CAS  Google Scholar 

  • Heikkila R.E., Youngster S.K., Manzino L., Cabbat F.S., and Duvoisin R.C. (1985b) Effect of 1 -methyl-4-phenyl- 1,2,3,6-tetrahydropyridine and related compounds on the uptake of [3H]3,4- dihydroxyphenylethylamine and [3H]5- hydroxytryptamine in neostriatal synaptosomal preparations. J. Neurochem. 44 310–313

    Article  PubMed  CAS  Google Scholar 

  • Javitch J.A. and Snyder S.H. (1984a) Uptake of MPP+ by domapine neurons explains selectivity of parkinsonism- inducing neurotoxin, MPTP. Eur. J. Pharmacol. 106 455–456

    Article  PubMed  CAS  Google Scholar 

  • Javitch J.A., Uhl G.R., and Snyder S.H. (1984b) Parkinson- ism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tet- rahydropyridine: Characterization and localization of receptor binding sites in rat and human brain. Proc. Natl. Acad. Sci. USA 81 4591–4595.

    Article  PubMed  CAS  Google Scholar 

  • Kinemuchi H., Arai Y., Oreland L., Tipton K.F., and Fowler C.J. (1982) Time-dependent inhibition of monoamine oxidase by β-phenylethylamine. Biochem. Pharmacol. 31 959–964.

    Article  PubMed  CAS  Google Scholar 

  • Kinemuchi H., Fowler C.J., and Tipton K.F. (1984) Substrate specificities of two forms of monoamine oxidase. In Monoamine oxidase and disease (Tipton K.F., Dostert P., and Strolin-Benedetti M. eds), pp.53–62.

    Google Scholar 

  • Langston J.W., Irwin I., and Langston E.B. (1984) Pargyline prevents MPTP-induced Parkinsonism in primates. Science 225 1480–1482.

    Article  PubMed  CAS  Google Scholar 

  • Langston J.W. (1985) MPTP and Parkinson’s disease. Trend in NeuroScience 8 79–83.

    Article  CAS  Google Scholar 

  • Markey S.P., Johannessen J.N., Chiueh C.C., Burns R.S., and Herkenham M.A. (1984) Intraneuronal generation of a pyridinium metabolite may cause drug-induced Parkinsonism. Nature (London) 311 464–467.

    Article  CAS  Google Scholar 

  • Markstein R., and Lahaye D. (1985) Neurochemical investigations in vitro with 1 -methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in preparations of rat brain. Eur. J. Pharmacol. 106 301–311.

    Article  Google Scholar 

  • Murphy D.L., Redmond D.E., Garrick N., and Baulu J. (1979) Monoamine oxidase type A and B activities in the vervet monkey. Neurochem. Res. 4 53–62

    Article  PubMed  CAS  Google Scholar 

  • Oreland L., Arai Y., Stenstrom A., and Fowler C.J. (1983) Monoamine oxidase and localisation in the brain and the activity in relation to psychiatric disorder. In Modern problems of pharmacopsychiatry (Beckman H., and Riederer P., eds) pp. 246–254, Karger, Basel.

    Google Scholar 

  • Orsi B.A. and Tipton K.F. (1979) Kinetic analysis of progress curves. In Methods in enzymology, 63A pp.159–183.

    Google Scholar 

  • Parsons B., and Rainbow T.C. (1984) High-affinity binding sites for [3H]MPTP may correspond to monoamine oxidase. Eur. J. Pharmacol. 102 375–377.

    Article  PubMed  CAS  Google Scholar 

  • Salach J.I., Singer T.P., Castagnol Jr.N., and Trevor A. (1984) Oxidation of the neurotoxic amine 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidase A and B and suicide inactivation of enzymes by MPTP. Biochem. Biophys. Res. Commun. 125 831–835.

    Article  PubMed  CAS  Google Scholar 

  • Tipton K.F. (1969) A sensitive fluorometric assay for monoamine oxidase. Analyt. Biochem. 28 318–325.

    Article  PubMed  CAS  Google Scholar 

  • Waley S.G. (1980) Kinetics of suicide substrate. Biochem. J. 185 771–773.

    PubMed  CAS  Google Scholar 

  • Wieczorek C.M., Parsons B., and Rainbow T.C. (1984) Quantitative autoradiography of [3H] MPTP binding sites in rat brain. Eur. J. Pharmacol. 98 453–454.

    Article  PubMed  CAS  Google Scholar 

  • Zigmond M.J. and Strieker E.M. (1984) Parkinson’s disease: Studies with an animal model. Life Sci. 35 5–18.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1985 The Humana Press Inc.

About this chapter

Cite this chapter

Kinemuchi, H., Arai, Y., Toyoshima, Y., Tadano, T., Kisara, K. (1985). Relations between MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine), the Neurotoxin MPP+ (1-Methyl-4-Phenylpyridinium Ion), and MAO in Rat Brain. In: Boulton, A.A., Maitre, L., Bieck, P.R., Riederer, P. (eds) Neuropsychopharmacology of the Trace Amines. Humana Press. https://doi.org/10.1007/978-1-4612-5010-4_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-5010-4_14

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-4612-9397-2

  • Online ISBN: 978-1-4612-5010-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics