The L ‐dopa on‐off effect in parkinson disease: Treatment by transient drug withdrawal and dopamine receptor resensitization

The L ‐dopa on‐off effect in parkinson disease: Treatment by transient drug withdrawal and... It has been suggested that patients with Parkinson disease partially compensate for neuron loss by developing denervation supersensitivity, and, if so, that prolonged levodopa (L‐dopa) therapy might lead to desensitization. As a preliminary test of this hypothesis, and in order to study whether it was possible to “resensitize” a patient who had already presumbly been desensitized by previous L‐dopa therapy, a patient who had become unpredictably responsive to L‐dopa was investigated. The patient had been taking L‐dopa for eight years and had exhibited severe dyskinesia‐akinesia oscillation (“on‐off” phenomenon) before the study. There was no consistent response to his hourly doses of Prolopa (L‐dopa and benserazide in a 4:1 ratio). He was first lowered, over 33 days, to 20% of his original Prolopa dose. The dosage was then increased until a consistent response were observed. The three main results achieved were, first, overall reduction by 64% of the daily requirement for L‐dopa; second, conversion from a previously unpredictable to a predictable response to each dose of L‐dopa; and, third, change in his movement fluctuations to a pattern more typical of “end‐of‐dose” akinesia than the “on‐off” phenomenon. The results support the idea of dopamine receptor resensitization upon reduction of the L‐dopa dosage. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

The L ‐dopa on‐off effect in parkinson disease: Treatment by transient drug withdrawal and dopamine receptor resensitization

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Publisher
Wiley
Copyright
Copyright © 1978 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
DOI
10.1002/ana.410040619
pmid
742858
Publisher site
See Article on Publisher Site

Abstract

It has been suggested that patients with Parkinson disease partially compensate for neuron loss by developing denervation supersensitivity, and, if so, that prolonged levodopa (L‐dopa) therapy might lead to desensitization. As a preliminary test of this hypothesis, and in order to study whether it was possible to “resensitize” a patient who had already presumbly been desensitized by previous L‐dopa therapy, a patient who had become unpredictably responsive to L‐dopa was investigated. The patient had been taking L‐dopa for eight years and had exhibited severe dyskinesia‐akinesia oscillation (“on‐off” phenomenon) before the study. There was no consistent response to his hourly doses of Prolopa (L‐dopa and benserazide in a 4:1 ratio). He was first lowered, over 33 days, to 20% of his original Prolopa dose. The dosage was then increased until a consistent response were observed. The three main results achieved were, first, overall reduction by 64% of the daily requirement for L‐dopa; second, conversion from a previously unpredictable to a predictable response to each dose of L‐dopa; and, third, change in his movement fluctuations to a pattern more typical of “end‐of‐dose” akinesia than the “on‐off” phenomenon. The results support the idea of dopamine receptor resensitization upon reduction of the L‐dopa dosage.

Journal

Annals of NeurologyWiley

Published: Dec 1, 1978

References

  • Levodopa‐induced dopamine receptor hypersensitivity
    Klawans, Klawans; Goetz, Goetz; Nausieda, Nausieda

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