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

Research output: Contribution to journalArticle

289 Citations (Scopus)

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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Adenosine A2 Receptor Antagonists
Levodopa
Parkinson Disease
Therapeutics
Placebos
Adenosine A2A Receptors
Antiparkinson Agents
Corpus Striatum
Dopamine Agents
Dyskinesias
Tremor
Drug-Related Side Effects and Adverse Reactions
Capsules
Animal Models
istradefylline
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Bara-Jimenez, W., Sherzai, A., Dimitrova, T., Favit, A., Bibbiani, F., Gillespie, 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
Bara-Jimenez, W. ; Sherzai, A. ; Dimitrova, T. ; Favit, A. ; Bibbiani, F. ; Gillespie, M. ; Morris, M. J. ; Mouradian, M Maral ; Chase, Thomas N. / Adenosine A2A receptor antagonist treatment of Parkinson's disease. In: Neurology. 2003 ; Vol. 61, No. 3. pp. 293-296.
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Bara-Jimenez, W, Sherzai, A, Dimitrova, T, Favit, A, Bibbiani, F, Gillespie, M, Morris, MJ, Mouradian, MM & Chase, TN 2003, 'Adenosine A2A receptor antagonist treatment of Parkinson's disease', Neurology, vol. 61, no. 3, pp. 293-296. https://doi.org/10.1212/01.WNL.0000073136.00548.D4

Adenosine A2A receptor antagonist treatment of Parkinson's disease. / Bara-Jimenez, W.; Sherzai, A.; Dimitrova, T.; Favit, A.; Bibbiani, F.; Gillespie, M.; Morris, M. J.; Mouradian, M Maral; Chase, Thomas N.

In: Neurology, Vol. 61, No. 3, 12.08.2003, p. 293-296.

Research output: Contribution to journalArticle

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AU - Bara-Jimenez, W.

AU - Sherzai, A.

AU - Dimitrova, T.

AU - Favit, A.

AU - Bibbiani, F.

AU - Gillespie, M.

AU - Morris, M. J.

AU - Mouradian, M Maral

AU - Chase, Thomas N.

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Bara-Jimenez W, Sherzai A, Dimitrova T, Favit A, Bibbiani F, Gillespie M et al. Adenosine A2A receptor antagonist treatment of Parkinson's disease. Neurology. 2003 Aug 12;61(3):293-296. https://doi.org/10.1212/01.WNL.0000073136.00548.D4