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Recent Advances in the Biochemical Pharmacology of Extrapyramidal Movement Disorders

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Parkinson’s Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 90))

Abstract

The biochemical pharmacology of parkinsonism and choreatic dis orders has been reviewed in relationship to recent observations in the synaptic pharmacology of dopaminergic systems. Despite the fact that parkinsonism is usually due to a failure of presynaptic dopamine input into the striatum, an identical clinical syndrome can result from postsynaptic striatal dysfunction. Although clinically identical, these two states differ both biochemically and pharmacologically. Presynaptic parkinsonism is associated with decreased dopamine turnover in the brain and responds to levodopa. Neither of these facts applies to postsynaptic parkinsonism

Denervation hypersensitivity has been proposed as a mechanism in the production of levodopa-induced dyskinesias and neurolepticinduced tardive dyskinesias. The role of chronic dopamine agonism in the former suggests that denervation hypersensitivity is not the only factor and raises the question that the treatment of parkinsonism with such agonists may inevitably be associated with dyskinesias and psychosis

Recent theories of the biochemical pharmacology of extrapyramidal movement disorders are largely derived from three separate sets of hypotheses:

  1. 1)

    Dopamine and acetylcholine have antagonistic effects on striatal neurons and that the normal function of these neurons depends upon a balance of the influences of these two neurotransmitters.

  2. 2)

    A shift of this balance such that there is a decrease in dopamine activity results in the signs and symptoms of parkinsonism. In most, if not all, of these patients this decrease is felt to come about as a result of decreased dopamine input (i.e., presynaptic dysfunction).

  3. 3)

    A shift of this balance such that there is a relative in crease in dopaminergic activity results in choreatic movement disorders. This increase in dopaminergic activity is felt to be due to dysfunction of the striatal neurons (postsynaptic dysfunction). This is felt to be related to primary neuronal disease in Huntington’s chorea and to denervation hypersensitivity in tardive dyskinesias and levodopa-induced dyskinesias.

These basic concepts are based on a wide diversity of clinical and preclinical observations which have been reviewed extensively (üornykiewiczy 1966, Klawans, 1968, Klawans et al., 1970, Klawans, 1973). Rather than review these data once again, this review will focus on selected recent observations which serve to qualify and redefine these basic premises. We will focus on three particular issues:

  1. 1)

    The occurrence of parkinsonism as a result of striatal cell dysfunction, i.e., postsynaptic parkinsonism.

  2. 2)

    The role of chronic dopaminergic agonism in the pathogenesis of levodopa-induced hypersensitivity, i.e., agonist-induced hypersensitivity.

  3. 3)

    Further observation on the development of denervation hypersensitivity within the central nervous system.

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Authors and Affiliations

  1. Division of Neurology, Michael Reese Hospital and Medical Center, Chicago, Illinois, USA

    Harold L. Klawans, Christopher Goetz, Paul A. Nausieda & William J. Weiner

  2. Department of Medicine (Neurology), University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA

    Harold L. Klawans, Paul A. Nausieda & William J. Weiner

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  1. Harold L. Klawans
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  2. Christopher Goetz
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  3. Paul A. Nausieda
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  4. William J. Weiner
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Editors and Affiliations

  1. Departments of Pharmacology and Therapeutics and Psychiatry, Texas Tech University School of Medicine, Lubbock, Texas, USA

    Fathy S. Messiha Ph. D. (Associate Professor, Chairman) (Associate Professor, Chairman)

  2. Department of Pharmacology and Therapeutics, Tarbox Parkinson’s Disease Institute, Texas Tech University School of Medicine, Lubbock, Texas, USA

    Alexander D. Kenny Ph. D. (Professor and Chairman, Acting Director) (Professor and Chairman, Acting Director)

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© 1977 Plenum Press, New York

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Klawans, H.L., Goetz, C., Nausieda, P.A., Weiner, W.J. (1977). Recent Advances in the Biochemical Pharmacology of Extrapyramidal Movement Disorders. In: Messiha, F.S., Kenny, A.D. (eds) Parkinson’s Disease. Advances in Experimental Medicine and Biology, vol 90. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-2511-6_2

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  • DOI: https://doi.org/10.1007/978-1-4684-2511-6_2

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