Exp Neurol 2000 Apr;162(2):321-7
Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA
or with selective D1 or D2 dopamine agonists increases antiparkinsonian
activity but not dyskinesia in MPTP-treated monkeys.
Kanda T, Jackson MJ, Smith LA, Pearce RK, Nakamura J, Kase H, Kuwana Y, Jenner
P
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari,
Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8731, Japan.
The novel selective adenosine A(2A) receptor antagonist KW-6002 improves motor disability in
MPTP-treated parkinsonian marmosets without provoking dyskinesia. In this study we have
investigated whether KW-6002 in combination with l-DOPA or selective D1 or D2 dopamine
receptor agonists enhances antiparkinsonian activity in MPTP-treated common marmosets.
Combination of KW-6002 with the selective dopamine D2 receptor agonist quinpirole or the D1
receptor agonist SKF80723 produced an additive improvement in motor disability.
Coadministration of KW-6002 with a low dose of L-DOPA also produced an additive
improvement in motor disability, and increased locomotor activity. The ability of KW-6002 to
enhance antiparkinsonian activity was more marked with L-DOPA and quinpirole than with the
D1 agonist. However, despite producing an enhanced antiparkinsonian response KW-6002 did
not exacerbate L-DOPA-induced dyskinesia in MPTP-treated common marmosets previously
primed to exhibit dyskinesia by prior exposure to L-DOPA. Selective adenosine A(2A) receptor
antagonists, such as KW-6002, may be one means of reducing the dosage of L-DOPA used in
treating Parkinson's disease and are potentially a novel approach to treating the illness both as
monotherapy and in combination with dopaminergic drugs. Copyright 2000 Academic Press. |
