Induction by dopamine D-1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease

Background: Dyskinesias are a frequent adverse effect of long-term levodopa therapy. The relative contribution of dopamine D-1 and D-2 receptor functi on to the pathophysiology of levodopa-induced dyskinesias remains a matter of controversy. Objective: To establish whether a selective D-2 dopamine agonist induces mo re or less dyskinesia than levodopa in primed dyskinetic patients with Park inson disease. Methods: We studied ABT-431, the prodrug of a fully selective D1 agonist, i n 20 subjects with advanced Parkinson disease and a fluctuating response to levodopa complicated by dyskinesias. Eight patients were studied in a doub le-blind, randomized design (French centers); 12, in an open, randomized de sign (US centers). We assessed and compared the antiparkinsonian (Unified P arkinson's Disease Rating Scale) and dyskinetic (response induced by an acu te challenge of a suprathreshold dose of levodopa and by 4 different ascend ing doses (5, 10, 20, and 40 mg) of ABT-431 during the 6 hours after the ch allenge. Results: The separate analysis of the double-blind and open data led to the same findings, ie, the antiparkinsonian and dyskinetic responses induced b y ABT-431 were dose related. At the most effective doses (20 and 40 mg), AB T-431 exhibited similar antiparkinsonian benefit and produced similar dyski nesias as levodopa. Conclusion: Dopamine D-2 agonists can induce a full antiparkinsonian respon se but do not support previous hypotheses suggesting that D-1 agonists are more or less likely to produce dyskinesias than levodopa.