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A hypothesis on the pathophysiological mechanisms that underlie levodopa- or dopamine agonist-induced dyskinesia in Parkinson's disease: implications for future strategies in treatment.
Mov Disord. 1990; 5(2):100-8.MD

Abstract

Long-term treatment of human Parkinson's disease with levodopa or dopamine agonists is often complicated by the appearance of abnormal involuntary movements (dyskinesias) that are extremely difficult to control. Little is known of the cause, pathophysiological mechanisms, or possible strategies for amelioration of this manifestation of dyskinesia. A hypothesis is set forth on the neural mechanisms that mediate levodopa- or dopamine agonist-induced dyskinesia (in particular chorea) as a side effect of the treatment of parkinsonism. Evidence is drawn from both clinical observations and experimental studies in a spectrum of movement disorders ranging from ballism through chorea to parkinsonism. It is proposed that (a) All forms of chorea, whatever their origin, share a common underlying neural mechanism. (b) Disordered activity of the subthalamic nucleus is central to the generation of choreic movements. In levodopa- or dopamine agonist-induced dyskinesia, (c) The site of action of dopaminergic agents in causing chorea is the putamen. (d) The specific pathophysiological state conducive to the appearance of chorea is brought about by the long-term exposure of the dopamine-depleted (parkinsonian) putamen to exogenous dopaminergic agents. (e) Long-term exposure to dopaminergic agents causes (either directly or indirectly) preferential inhibition of the subpopulation of putaminal neurones that project specifically to the lateral segment of the globus pallidus. This causes disinhibition of lateral pallidal neurones, which become overactive and physiologically inhibit the subthalamic nucleus. (f) The hypothesis suggests a number of possible strategies that might be useful for the alleviation of levodopa-induced dyskinesia.

Authors+Show Affiliations

Department of Cell and Structural Biology, Medical School, University of Manchester, England, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

1970120

Citation

Crossman, A R.. "A Hypothesis On the Pathophysiological Mechanisms That Underlie Levodopa- or Dopamine Agonist-induced Dyskinesia in Parkinson's Disease: Implications for Future Strategies in Treatment." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 5, no. 2, 1990, pp. 100-8.
Crossman AR. A hypothesis on the pathophysiological mechanisms that underlie levodopa- or dopamine agonist-induced dyskinesia in Parkinson's disease: implications for future strategies in treatment. Mov Disord. 1990;5(2):100-8.
Crossman, A. R. (1990). A hypothesis on the pathophysiological mechanisms that underlie levodopa- or dopamine agonist-induced dyskinesia in Parkinson's disease: implications for future strategies in treatment. Movement Disorders : Official Journal of the Movement Disorder Society, 5(2), 100-8.
Crossman AR. A Hypothesis On the Pathophysiological Mechanisms That Underlie Levodopa- or Dopamine Agonist-induced Dyskinesia in Parkinson's Disease: Implications for Future Strategies in Treatment. Mov Disord. 1990;5(2):100-8. PubMed PMID: 1970120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A hypothesis on the pathophysiological mechanisms that underlie levodopa- or dopamine agonist-induced dyskinesia in Parkinson's disease: implications for future strategies in treatment. A1 - Crossman,A R, PY - 1990/1/1/pubmed PY - 1990/1/1/medline PY - 1990/1/1/entrez SP - 100 EP - 8 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 5 IS - 2 N2 - Long-term treatment of human Parkinson's disease with levodopa or dopamine agonists is often complicated by the appearance of abnormal involuntary movements (dyskinesias) that are extremely difficult to control. Little is known of the cause, pathophysiological mechanisms, or possible strategies for amelioration of this manifestation of dyskinesia. A hypothesis is set forth on the neural mechanisms that mediate levodopa- or dopamine agonist-induced dyskinesia (in particular chorea) as a side effect of the treatment of parkinsonism. Evidence is drawn from both clinical observations and experimental studies in a spectrum of movement disorders ranging from ballism through chorea to parkinsonism. It is proposed that (a) All forms of chorea, whatever their origin, share a common underlying neural mechanism. (b) Disordered activity of the subthalamic nucleus is central to the generation of choreic movements. In levodopa- or dopamine agonist-induced dyskinesia, (c) The site of action of dopaminergic agents in causing chorea is the putamen. (d) The specific pathophysiological state conducive to the appearance of chorea is brought about by the long-term exposure of the dopamine-depleted (parkinsonian) putamen to exogenous dopaminergic agents. (e) Long-term exposure to dopaminergic agents causes (either directly or indirectly) preferential inhibition of the subpopulation of putaminal neurones that project specifically to the lateral segment of the globus pallidus. This causes disinhibition of lateral pallidal neurones, which become overactive and physiologically inhibit the subthalamic nucleus. (f) The hypothesis suggests a number of possible strategies that might be useful for the alleviation of levodopa-induced dyskinesia. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/1970120/A_hypothesis_on_the_pathophysiological_mechanisms_that_underlie_levodopa__or_dopamine_agonist_induced_dyskinesia_in_Parkinson's_disease:_implications_for_future_strategies_in_treatment_ DB - PRIME DP - Unbound Medicine ER -
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