Journal of Pharmacological Sciences (Print Edition) 2007-03-01

Synergistic effects of adenosine A2A antagonist and L-DOPA on rotational behaviors in 6-hydroxydopamine-induced hemi-Parkinsonian mouse model.

Takahiro Matsuya, Kazuhiro Takuma, Kosuke Sato, Makoto Asai, Yoshihiro Murakami, Sosuke Miyoshi, Akihiro Noda, Taku Nagai, Hiroyuki Mizoguchi, Shintaro Nishimura, Kiyofumi Yamada

Index: J. Pharm. Sci. 103 , 329-332, (2007)

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Abstract

In this study, we examined the combination effects of L-DOPA and adenosine receptor antagonists on rotational behaviors in a hemi-Parkinsonian mouse model induced by unilateral 6-hydroxydopamine (6-OHDA) injection. The adenosine A(2A) antagonist SCH-58261, but not the A(1)-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or A(2B)-receptor antagonist alloxazine, synergistically potentiated the L-DOPA-induced rotational behaviors in the 6-OHDA-lesioned mice. In addtion, the 6-OHDA-induced lesions of the dopaminergic system did not affect the in vivo binding of an adenosine A(2A)-receptor tracer [(11)C]SCH-442416 in the striatatum. These findings suggest that adenosine A(2A) antagonists are extremely useful for pharmacotherapy of L-DOPA in Parkinson's disease patients.