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 Kase, H. Search for Related Content PubMed PubMed Citation Articles by Kase, H.

Neurology supplements are not peer-reviewed.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.

Industry forum: Progress in pursuit of therapeutic A_2A antagonists

The adenosine A_2A receptor selective antagonist KW6002: Research and development toward a novel nondopaminergic therapy for Parkinson’s disease

From Kyowa Hakko Kogyo Co. Ltd., Tokyo, Japan.

Address correspondence and reprint requests to Dr. Hiroshi Kase, Kyowa Hakko Kogyo Co., Ltd., 1-6-1 Ohtemachi, Chiyodaku, Tokyo 100-8185, Japan; e-mail: hiroshi.kase{at}kyowa.co.jp

Research and development of the adenosine A_2A receptor selective antagonist KW6002 have focused on developing a novel nondopaminergic therapy for Parkinson’s disease (PD). Salient pharmacologic features of KW6002 were investigated in several animal models of PD. In rodent and primate models, KW6002 provides symptomatic relief from parkinsonian motor deficits without provoking dyskinesia or exacerbating existing dyskinesias. The major target neurons of the A_2A receptor antagonist were identified as GABAergic striatopallidal medium spiny neurons. A possible mechanism of A_2A receptor antagonist action in PD has been proposed based on the involvement of striatal and pallidal presynaptic A_2A receptors in the "dual" modulation of GABAergic synaptic transmission. Experiments with dopamine D₂ receptor knockout mice showed that A_2A receptors can function and anti-PD activities of A_2A antagonists can occur independent of the dopaminergic system. Clinical studies of KW6002 in patients with advanced PD with L-dopa–related motor complications yielded promising results with regard to motor symptom relief without motor side effects. The development of KW6002 represents the first time that a concept gleaned from A_2A biologic research has been applied successfully to "proof of concept" clinical studies. The selective A_2A antagonist should provide a novel nondopaminergic approach to PD therapy.

This article has been cited by other articles:

				F. S. Jones, J. Jing, A. H. Stonehouse, A. Stevens, and G. M. Edelman Caffeine Stimulates Cytochrome Oxidase Expression and Activity in the Striatum in a Sexually Dimorphic Manner Mol. Pharmacol., September 1, 2008; 74(3): 673 - 684. [Abstract] [Full Text] [PDF]

				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]

				J. Mojsilovic-Petrovic, G.-B. Jeong, A. Crocker, A. Arneja, S. David, D. Russell, and R. G. Kalb Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors J. Neurosci., September 6, 2006; 26(36): 9250 - 9263. [Abstract] [Full Text] [PDF]