TY - JOUR
T1 - Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease
AU - Rascol, O.
AU - Nutt, J. G.
AU - Blin, O.
AU - Goetz, C. G.
AU - Trugman, J. M.
AU - Soubrouillard, C.
AU - Carter, J. H.
AU - Currie, L. J.
AU - Fabre, N.
AU - Thalamas, C.
AU - Giardina, W. J.
AU - Wright, S.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1001/archneur.58.2.249
DO - 10.1001/archneur.58.2.249
M3 - Article
C2 - 11176963
AN - SCOPUS:0034745615
SN - 0003-9942
VL - 58
SP - 249
EP - 254
JO - Archives of Neurology
JF - Archives of Neurology
IS - 2
ER -