HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jenner, P. Search for Related Content PubMed PubMed Citation Articles by Jenner, P.

Neurology supplements are not peer-reviewed. Information contained in Neurology supplements represent the opinions of the authors and are not endorsed by nor do they reflect the views of the American Academy of Neurology, Editor-in-Chief, or Associate Editors of Neurology.

A_2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD

From the Neurodegenerative Diseases Research Centre, Guy’s, King’s and St. Thomas’ School of Biomedical Sciences, King’s College, London, UK.

Address correspondence and reprint requests to Dr. Peter Jenner, Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King’s College, London SE1 1UL, UK; e-mail: peter.jenner{at}kcl.ac.uk

The future management of Parkinson’s disease (PD) requires pharmacologic agents that do not lose efficacy with disease progression or induce dyskinesia and that are free of other dopaminergic side effects. A_2A receptor antagonists may provide an opportunity to introduce nondopaminergic management of PD. A_2A receptors are selectively localized in basal ganglia and to the indirect output pathway where they control GABA and acetylcholine release. The A_2A antagonists are effective in rodent models of PD, reversing motor deficits in haloperidol-treated, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated, or reserpinized mice, and potentiating L-dopa–induced rotation in 6-hydroxydopamine–lesioned rats without inducing dyskinesia. Importantly, the selective A_2A antagonist KW6002 reverses motor disability and increases locomotor activity in MPTP-treated primates without provoking dyskinesia established by previous exposure to L-dopa. In addition, KW6002 shows additive antiparkinsonian activity with L-dopa and the D₂ agonist quinpirole in MPTP-treated primates without enhancing the intensity of dyskinesia. The data available suggest that A_2A antagonists, such as KW6002, may be effective as monotherapy for the management of PD and that they will also produce additional benefit when administered in combination with L-dopa or dopamine agonist therapy.

This article has been cited by other articles:

				D. Xiao, E. Bastia, Y.-H. Xu, C. L. Benn, J.-H. J. Cha, T. S. Peterson, J.-F. Chen, and M. A. Schwarzschild Forebrain Adenosine A2A Receptors Contribute to L-3,4-Dihydroxyphenylalanine-Induced Dyskinesia in Hemiparkinsonian Mice J. Neurosci., December 27, 2006; 26(52): 13548 - 13555. [Abstract] [Full Text] [PDF]