This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (40)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Movement Disorders  • Parkinson Disease/ Parkinsonian Disorders  • Drug Therapy  • Adverse Effects  • Alert me on articles by topic

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

Arch Neurol. 2001;58:249-254.

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 D₁ 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 D₁ 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 D₁ agonists can induce a full antiparkinsonian response but do not support previous hypotheses suggesting that D₁ agonists are more or less likely to produce dyskinesias than levodopa.

From the Clinical Investigation Centre, Departments of Neurology and Pharmacology, Institut National de la Santé et de la Recherce Médicale U 455, Toulouse University Hospital, Toulouse, France (Drs Rascol, Fabre, and Thalamas); the Department of Neurology, Oregon Health Sciences University, Portland (Drs Nutt and Carter); the Centre of Clinical Pharmacology and Experimental Therapeutics, Marseille University Hospital, Marseille, France (Drs Blin and Soubrouillard); the Section of Movement Disorders, Department of Neurological Sciences, Rush–Presbyterian–St Luke's Hospital, Chicago, Ill (Dr Goetz); the Department of Neurology, University of Virginia Health Sciences Center, Charlottesville (Drs Trugman and Currie); and Neurological and Urological Diseases Research, Abbott Laboratories, Abbott Park, Ill (Drs Giardina and Wright). Drs Rascol and Blin received a consultancy honorarium from Abbott Laboratories to conduct this trial.

Corresponding author and reprints: O. Rascol, MD, PhD, Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, 37 Allées Jules Guesde, 31073 Toulouse Cedex, France (e-mail: rascol{at}cict.fr).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Avoidance of dyskinesia: Preclinical evidence for continuous dopaminergic stimulation
Jenner
Neurology 2004;62:S47-55.
ABSTRACT | FULL TEXT  

The MPTP-treated primate as a model of motor complications in PD: Primate model of motor complications
Jenner
Neurology 2003;61:S4-11.
ABSTRACT | FULL TEXT  

Pharmacology of dopamine agonists in the treatment of Parkinson's disease
Jenner
Neurology 2002;58:S1-8.
ABSTRACT | FULL TEXT