title: The L-dopa on-off effect in Parkinson disease: treatment by transient drug withdrawal and dopamine receptor resensitization.
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 presumably 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 was 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.
mesh_terms: D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000139:chemically induced; D010300:Parkinson Disease / Q000188:drug therapy*; D011954:Receptors, Dopamine / Q000187:drug effects*
chemical_list: D011954:Receptors, Dopamine; D007980:Levodopa