Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease

O. Rascol, J. G. Nutt, O. Blin, C. G. Goetz, J. M. Trugman, C. Soubrouillard, J. H. Carter, L. J. Currie, N. Fabre, C. Thalamas, W. J. Giardina, S. Wright

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116 Scopus citations

Abstract

Background: Dyskinesias are a frequent adverse effect of long-term levodopa therapy. The relative contribution of dopamine D1 and D2 receptor function to the pathophysiology of levodopa-induced dyskinesias remains a matter of controversy. Objective: To establish whether a selective Dt dopamine agonist induces more or less dyskinesia than levodopa in primed dyskinetic patients with Parkinson disease. Methods: We studied ABT-431, the prodrug of a fully selective Dt agonist, in 20 subjects with advanced Parkinson disease and a fluctuating response to levodopa complicated by dyskinesias. Eight patients were studied in a double-blind, randomized design (French centers); 12, in an open, randomized design (US centers). We assessed and compared the antiparkinsonian (Unified Parkinson's Disease Rating Scale) and dyskinetic (response induced by an acute challenge of a suprathreshold dose of levodopa and by 4 different ascending doses (5, 10, 20, and 40 mg) of ABT-431 during the 6 hours after the challenge. Results: The separate analysis of the double-blind and open data led to the same findings, ie, the antiparkinsonian and dyskinetic responses induced by ABT-431 were dose related. At the most effective doses (20 and 40 mg), ABT-431 exhibited similar antiparkinsonian benefit and produced similar dyskinesias as levodopa. Conclusion: Dopamine Dt agonists can induce a full antiparkinsonian response but do not support previous hypotheses suggesting that Dt agonists are more or less likely to produce dyskinesias than levodopa.

Original languageEnglish (US)
Pages (from-to)249-254
Number of pages6
JournalArchives of Neurology
Volume58
Issue number2
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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