Synergistic effects of adenosine A2A antagonist and L-DOPA on rotational behaviors in 6-hydroxydopamine-induced hemi-Parkinsonian mouse model.
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.
Matsuya
Takahiro
T
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan.
Takuma
Kazuhiro
K
Sato
Kosuke
K
Asai
Makoto
M
Murakami
Yoshihiro
Y
Miyoshi
Sosuke
S
Noda
Akihiro
A
Nagai
Taku
T
Mizoguchi
Hiroyuki
H
Nishimura
Shintaro
S
Yamada
Kiyofumi
K
D058917:Adenosine A2 Receptor Antagonists; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004357:Drug Synergism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D011743:Pyrimidines / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D043705:Receptor, Adenosine A2A / Q000627:therapeutic use; D012399:Rotation; D014230:Triazoles / Q000037:antagonists & inhibitors / Q000627:therapeutic use
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; D007980:Levodopa; D016627:Oxidopamine