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Dopaminergic Systems and their Regulation pp 243–259Cite as

Palgrave Macmillan

Dopamine Neurone Destruction in Human and Animal Parkinsonism

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Abstract

The cause of Parkinson’s disease is unknown. The motor deficits of the illness are associated with a profound loss of dopamine containing neurones throughout the brain. However, postmortem studies suggest that alterations also occur in other neuronal systems including those utilising noradrenaline, 5HT, GABA, acetylcholine and neuropeptides. The primary role played by the deficit in brain dopamine content is emphasised by the ability of L-DOPA or dopamine agonist drugs to reverse the motor symptoms. However, for reasons which are unclear, the initial benefit of L-DOPA often wanes so that the long-term treatment of Parkinson’s disease is complicated by a loss of drug effect.

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References

  • Barbeau,A., Sourkes,T.L. and Murphy,G. (1962). Les catecholamines dans la maladie de Parkinson. In Monoamines et Systeme Nerveux Central. (ed.J.de Ajuriaguerra). Georg, Geneve & Masson, Paris. pp.247–262.

    Google Scholar 

  • Bauman,R.J., Jameson,H.D., Weisberg,L.H., McKean,H.E. and Haack, D.G. (1980). Cigarette smoking and Parkinson’s disease. Neurology 30,839–843.

    Article  Google Scholar 

  • Birkmayer,W. and Hornykiewicz,O. (1961). Der L-Dioxyphenylalanin (= L-DOPA) — Effekt bei der Parkinson-Akinese. Wien.Klin.Wochensch., 73,787–788.

    CAS  Google Scholar 

  • Boyce,S., Kelly,E., Reavill,C., Jenner,P. and Marsden,C.D. (1984). Repeated administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to rats is not toxic to striatal dopamine neurones. Biochem.Pharmac., 23,1747–1752.

    Article  Google Scholar 

  • Bradbury,A.J., Costall,B., Domeney,A.M., Jenner,P., Marsden,C.D. and Naylor,R.J. (1984). MPTP infusion into rat substantia nigra causes hypokinesia and bradykinesia, which are reversed by L-DOPA treatment. Presented at Dopamine 84, Southampton.

    Google Scholar 

  • Burns,R.S., Chiueh,C.C., Markey,S.P., Ebert,M.H., Jacobowitz,D.M. and Kopin,I.J. (1983). A primate model of Parkinsonism: Selective destruction of dopaminergic neurones in the pars compacta of the substantia nigra by N-metyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc.Natl.Acad.Sci.U.S.A., 80,4546–4550.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Burns,R.S., Markey,S.P., Phillips,J.M. and Chiueh,C.C. (1984). The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the monkey and man. Can.J.Neurol.Sci.,11,Suppl. 1,166–168.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Chiueh,C.C., Markey,S.P., Burns,R.S., Johanessen,J.N., Pert,A. and Bopin,I.J. (1984) Neurochemical and behavioural effects of systemic and intranigral administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the rat. Eur.J.Pharmac., 100,189–194.

    Article  CAS  Google Scholar 

  • Cotzias,G.C., Papavasiliou,P.J., van Woert,M.H. and Sakamoto,A. (1964). Melanogenesis and extrapyramidal disease. Fed.Proc., 23,713–718.

    PubMed  CAS  Google Scholar 

  • Cotzias,G.C., van Woert,M.H. and Schiffer,L.M. (1967). Aromatic amino acids and modification of Parkinsonism. New Engl.J.Med., 276, 374–379.

    Article  PubMed  CAS  Google Scholar 

  • Davis,G.C., Williams,A.C., Markey,S.P., Ebert,M.H., Caine,E.D., Reichert,C.M. and Kopin,I.J. (1979). Chronic Parkinsonism secondary to intravenous injection of mepiridine analogues. Psychiat.Res., 1, 249–254.

    Article  CAS  Google Scholar 

  • Denton,T. and Howard,B.D. (1984) Inhibition of dopamine uptake by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a cause of Parkinson-ism. Biochem,Biophys.Res.Comm., 119,1186–1190,

    Google Scholar 

  • Duvoisin,R.C., Eldridge,R., Williams,A., Nutt,J. and Calne,D. (1981). Twin study of Parkinson’s disease. Neurology 31,77–80.

    Article  PubMed  CAS  Google Scholar 

  • Ehringer,H. and Hornykiewicz,O. (1960) Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschene und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin, Wochensch., 38,1238–1239.

    Article  Google Scholar 

  • Forno,L.S. (1982). Pathology of Parkinson’s Disease. In Movement Disorders. (Eds.C.D.Marsden and S.Fahn). Butterworth Scientific, London. pp.25–40,

    Google Scholar 

  • Graham,D.G. (1979). On the origin and significance of neuromelanin. Arch.Path.Lab.Med., 103,359–362.

    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 neurones in the mouse. Eur.J.Pharmacol., 97, 133–136.

    Article  PubMed  CAS  Google Scholar 

  • Heikkila,R.E., Cabbat,F,S., Manzino,L. and Duvoisin,R.C. (1984). Effects of l-methyl-4-phenyl-1,2,5,6-tetrahydropyridine on neostriatal dopamine in mice. Neuropharmacology 3,711–713. Heikkila,R,E.,

    Google Scholar 

  • Manzino,L., Cabbat,F.S. and Duvoisin,R.C. (1984b). Protection against the dopaminergic neurotoxicity of l-methyl-4-phenyl-1,2,3,Ertetrahydropyridine by monoamineoxidase inhibitors. Nature 311,467–469.

    Article  PubMed  Google Scholar 

  • Hornykiewicz,O. (1982). Brain neurotransmitter changes in Parkinson’s disease. In Movement Disorders. (Eds.C.D.Marsden and S.Fahn). Butterworth Scientific, London. pp,41–58.

    Google Scholar 

  • Javitch,J,A,, Uhl,G.R. and Snyder,S.H. (1984). Parkinsonism-inducing neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: Characterisation and localisation of receptor binding sites in rat and human brain. Proc.Natl.Acad.Sci.U.S,A., 81,4591–4595.

    Article  CAS  Google Scholar 

  • Javoy-Agid,F., Taquet,H., Cesselin,F., Epelbaum,J., Grouselle,D., Mauborgne,A., Studler,J.M. and Agid,Y. (1984). Neuropeptides in Parkinson’s disease. In Catecholamines: Part C Neuropharmacology and Central Nervous Sytems — Therapeutic Aspects, Alan R.Liss,Inc. New York, pp.35–42.

    Google Scholar 

  • Jenner,P., Sheehy,M.P. and Marsden,C.D. (1983). Noradrenaline and 5-hydroxytryptamine modulation of brain dopamine function: Implications for the treatment of Parkinson’s disease. Brit.J,Clin, Pharmacol.,15,Suppl.2,2775–2895.

    Google Scholar 

  • Jenner,P., Rupniak,N.M.J., Rose,S., Kelly,E,, Kilpatrick,G., Lees, A. and Marsden,C.D. (1984). l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in the common marmoset. Neurosci. Lett., 50,85–90.

    Google Scholar 

  • Kula,N.S., Baldessarini,R.J., Campbell,A., Finklestein,S., Ram,V.J. and Neumeyer,J.L. (1984). Effects of N-substituted phenyltetra-hydropyridines on cerebral high-affinity synaptosomal uptake of dopamine and other monoamines in several mammalian species. Life Sci., 34,2567–2575.

    Article  PubMed  CAS  Google Scholar 

  • Langston,J.W., Ballard,P., Tetrud,J,W, and Irwin,I, (1983), Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219,979–980.

    Article  PubMed  CAS  Google Scholar 

  • Langston,J.W., Langston,E.B. and Irwin,I. (1984a). MPTP-induced Parkinsonism in human and non-human primates — Clinical and experimental aspects. Acta Neurol.Scand.,70,Suppl. 100,49–54.

    Google Scholar 

  • Langston,J.W, and Ballard,P.A.Jr. (1984b). Parkinsonism induced by l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): Implications for treatment and the pathogenesis of Parkinson’s disease. Canad. J.Neurol.Sci.,11,Suppl. 1,160–165.

    PubMed  CAS  Google Scholar 

  • Langston,J.W., Forno,L.S., Rebert,C.S. and Irwin,I. (1984c) Selective nigral toxicity after systemic administration of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the squirrel monkey. Brain Res., 292,390–495.

    Article  PubMed  CAS  Google Scholar 

  • Langston,J.W., Irwin,I., Langston,E.B. and Forno,L.S. (1984d) The importance of the ‘4–5’ double bond for neurotoxicity in primates of the pyridine derivative MPTP. Neurosci.Lett., 50,289–294.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lyden,A., Bondesson,U., Larsson,B.S. and Lindquist,N.G. (1983). Melanin affinity of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, an inducer of chronic Parkinsonism in humans. Acta Pharmacol.Toxicol. 53,429–432.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Marsden,C.D., Parkes,J.D. and Quinn,N. (1982). Fluctuations of disability in Parkinson’s disease — Clinical aspects. In Movement Disorders. (Eds. C.D.Marsden and S.Fahn). Butterworth Scientific, London. pp.96–122.

    Google Scholar 

  • Marsden,C.D. (1983). Neuromelanin and Parkinson’s disease. J.Neural. Trans.Suppl., 19,121–141.

    CAS  Google Scholar 

  • Palacios,J.M. and Wiederhold,K.H. (1984). Acute administration of l-N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a compound producing Parkinsonism in humans, stimulates (2-14C)-deoxyglucose uptake in the regions of the catecholaminergic cell bodies in the rat and guinea pig brains. Brain Res., 301,187–191.

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  • Rinne,U.K. (1982). Brain neurotransmitter receptors in Parkinson’s disease. In Movement Disorders. (Eds.C.D.Marsden and S.Fahn). Butterworth Scientific, London. pp.59–74.

    Google Scholar 

  • Saghal,A., Andrews,J.S., Biggins,J.A., Cand,J.M., Edwardson,J.A., Keith,A.B., Turner,J.D. and Wright,C. (1984). N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) affects locomotor activity without producing a nigro-striatal lesion in the rat. Neurosci.Lett., 48,179–184.

    Article  Google Scholar 

  • Schmidt,C.J., Matsuda,L.A. and Gibb,J.W. (1984) In vitro release for tritiated monoamines from rat CNS tissue by the neurotoxic compound l-methyl-phenyl-tetrahydropyridine. Eur.J.Pharmacol., 103,255–260.

    Google Scholar 

  • Steranka,L.R., Polite,L.N., Perry,K.W. and Fuller,R.W. (1983). Dopamine depletion in rat brain by MPTP (l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Bes.Comm.Substances Abuse 4,315–322.

    CAS  Google Scholar 

  • Wieczorek,C.M., Parsons,B. and Rainbow,T.C. (1984). Quantitative autoradiography of 3R-MPTO binding sites in rat brain. Fkir.J. Pharmacol., 98, 453–454.

    CAS  Google Scholar 

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Authors
  1. P. Jenner
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  2. C. D. Marsden
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Editor information

Editors and Affiliations

  1. Merck Sharp and Dohme Research Laboratories, Harlow, Essex, UK

    G. N. Woodruff (Director of Pharmacology) (Director of Pharmacology)

  2. Department of Physiology and Pharmacology, University of Southampton, UK

    J. A. Poat  & P. J. Roberts  & 

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© 1986 The Contributors

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Jenner, P., Marsden, C.D. (1986). Dopamine Neurone Destruction in Human and Animal Parkinsonism. In: Woodruff, G.N., Poat, J.A., Roberts, P.J. (eds) Dopaminergic Systems and their Regulation. Satellite Symposia of the IUPHAR 9th International Congress of Pharmacology. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-07431-0_16

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  • DOI: https://doi.org/10.1007/978-1-349-07431-0_16

  • Publisher Name: Palgrave Macmillan, London

  • Print ISBN: 978-1-349-07433-4

  • Online ISBN: 978-1-349-07431-0

  • eBook Packages: MedicineMedicine (R0)

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