Adenosine A2A Antagonist: A novel antiparkinsonian agent that does not provoke dyskinesia in Parkinsonian monkeys

✍ Scribed by Tomoyuki Kanda; Michael J. Jackson; Lance A. Smith; Ronald K. B. Pearce; Joji Nakamura; Hiroshi Kase; Yoshihisa Kuwana; Prof Peter Jenner

• Book ID: 102707915
• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 756 KB
• Volume: 43
• Category: Article
• ISSN: 0364-5134
• DOI: 10.1002/ana.410430415

✦ Synopsis

s disease with L-dopa therapy leads to long-term complications, including loss of drug efficacy and the onset of dyskinesia. Adenosine A2A receptors in striatum are selectively localized to GABAergic output neurons of the striato-pallidal pathway and may avoid such problems. The novel adenosine AzA receptor antagonist KW-6002 has been examined for antiparkinsonian activity in MPTP-treated primates. Oral administration of KW-6002 reversed motor disability in MPTP-treated common marmosets in a dose-dependent manner. However, KW-6002 only modestly increased overall locomotor activity and did not cause abnormal movement, such as stereotypy. The ability of KW-6002 to reverse motor disability was maintained on repeated daily administration for 21 days, and no tolerance was observed. KW-6002 induced little or no dyskinesia in MPTP-treated primates previously primed to exhibit dyskinesia by prior exposure to L-dopa. These results suggest that selective adenosine A2A receptor antagonists represent a new class of antiparkinsonian agents that improve disability without producing hyperactivity and without inducing dyskinesia.