Adenosine A2A receptor antagonist treatment of Parkinson's disease

W. Bara-Jimenez, A. Sherzai, T. Dimitrova, A. Favit, F. Bibbiani, M. Gillespie, M. J. Morris, M Maral Mouradian, Thomas N. Chase

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Abstract

Background: Observations in animal models suggest that A2A antagonists confer benefit by modulating dopaminergic effects on the striatal dysfunction associated with motor disability. This double-blind, placebo-controlled, proof-of-principle study evaluated the pathogenic contribution and therapeutic potential of adenosine A2A receptor-mediated mechanisms in Parkinson disease (PD) and levodopa-induced motor complications. Methods: Fifteen patients with moderate to advanced PD consented to participate. All were randomized to either the selective A 2A antagonist KW-6002 or matching placebo capsules in a 6-week dose-rising design (40 and 80 mg/day). Motor function was rated on the Unified PD Rating Scale. Results: KW-6002 alone or in combination with a steady-state IV infusion of each patient's optimal levodopa dose had no effect on parkinsonian severity. At a low dose of levodopa, however, KW-6002 (80 mg) potentiated the antiparkinsonian response by 36% (p < 0.02), but with 45% less dyskinesia compared with that induced by optimal dose levodopa alone (p < 0.05). All cardinal parkinsonian signs improved, especially resting tremor. In addition, KW-6002 prolonged the efficacy half-time of levodopa by an average of 47 minutes (76%; p < 0.05). No medically important drug toxicity occurred. Conclusions: The results support the hypothesis that A2A receptor mechanisms contribute to symptom production in PD and that drugs able to selectively block these receptors may help palliate symptoms in levodopa-treated patients with this disorder.

Original languageEnglish (US)
Pages (from-to)293-296
Number of pages4
JournalNeurology
Volume61
Issue number3
DOIs
StatePublished - Aug 12 2003

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All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Bara-Jimenez, W., Sherzai, A., Dimitrova, T., Favit, A., Bibbiani, F., Gillespie, M., Morris, M. J., Mouradian, M. M., & Chase, T. N. (2003). Adenosine A2A receptor antagonist treatment of Parkinson's disease. Neurology, 61(3), 293-296. https://doi.org/10.1212/01.WNL.0000073136.00548.D4