Objective: The aim of this study was to assess the anxiolytic effects of istradefylline (KW-6002), an adenosine A_2A receptor antagonist, in naive and anxiety-prone animals using various experimental models of anxiety.

Background: Istradefylline is an antiParkinsonian agent and improves the motor symptoms in patients with Parkinson’s disease (PD). Anxiety and depression are common features of PD. We have already reported that istradefylline is effective in animal models of depression (Pharmacol Biochem Behav. 2013;114-115:23-30; Psychopharmacology 2014;231:2839-49). However, the effects of istradefylline on anxiety have not been determined.

Methods: We conducted the elevated plus maze, social interaction and maternal separation tests in naive rats, as well as in the marble burying, hole-board and novelty suppressed feeding tests in naive mice. We also performed the elevated plus maze test in anxiety-prone rats induced by repeated ethanol administration and subsequent withdrawal from the treatment.

Results: Acutely administered istradefylline alone exerted anxiolytic-like effects in all of the tests in rats and mice. In addition, Co-administration of sub-threshold doses of istradefylline with an existing anxiolytic was also effective in some of the tests. Moreover, istradefylline reduced anxiety-like behaviors of the anxiety-prone rats in the elevated plus maze test.

Conclusions: The results suggest that istradefylline possesses anxiolytic activity as well as antiParkinsonian activity, leading to benefits to patients with PD by both reducing anxiety and improving motor function. Furthermore, blockade of adenosine A_2A receptors may provide a novel strategy for treating general anxiety disorders including those caused by alcohol withdrawal.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/anxiolytic-like-activity-of-the-adenosine-a2a-receptor-antagonist-istradefylline-kw-6002-in-rodent-models-of-anxiety/