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The L ‐dopa on‐off effect in parkinson disease: Treatment by transient drug withdrawal and dopamine receptor resensitization
Author(s) -
Direnfeld L.,
Spero L.,
Marotta J.,
Seeman P.
Publication year - 1978
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410040619
Subject(s) - benserazide , levodopa , dopamine , dyskinesia , medicine , parkinson's disease , carbidopa , drug holiday , drug , pharmacology , denervation , dopamine receptor , desensitization (medicine) , disease , receptor , psychology , neuroscience , immunology , human immunodeficiency virus (hiv)
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.