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Effects of L-dopa metabolites at a dopamine receptor suggest a basis for ‘on-off’ effect in Parkinson's disease

Abstract

ALTHOUGH L-dopa is the most effective therapeutic agent available for the control of the akinesia of Parkinson's disease, long term therapy may be associated with a variety of therapeutic problems1. One problem seen in some patients is a progressive loss of therapeutic response which may be associated with abnormal involuntary movements1. A state may develop in which a good response to the drug alternates with periods of akinesia and rigidity1–4. This has been called the ‘on-off’ effect or akinesia paradoxica1. While low blood levels of L-dopa may explain the onset of akinesia (‘off’ effect), this cannot explain the sudden reversal of patients' akinesia (‘on’ effect) which may occur without additional dosage of L-dopa2,3.

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DOUGAN, D., WADE, D. & MEARRICK, P. Effects of L-dopa metabolites at a dopamine receptor suggest a basis for ‘on-off’ effect in Parkinson's disease. Nature 254, 70–72 (1975). https://doi.org/10.1038/254070a0

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