Combined use of the adenosine A2A antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys
Combined use of the adenosine A2A antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys
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DOI：
10.1006/exnr.2000.7350
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发表时间：
2000-04-01
影响因子：
5.3
通讯作者：
Jenner, P
中科院分区：
文献类型：
--
作者：
Kanda, T;Jackson, MJ;Jenner, P
新型选择性腺苷A(2A)受体拮抗剂KW-6002改善了MPTP治疗的帕金森病恒河猴的运动障碍，而不会引起运动障碍。在这项研究中，我们研究了KW-6002与L-多巴或选择性的D1或D2多巴胺受体激动剂联合使用是否能增强MPTP治疗的普通恒河猴的抗帕金森病活性。KW-6002与选择性多巴胺Ha受体激动剂奎匹罗或D1受体激动剂SKF80723相结合，可进一步改善运动障碍。联合服用KW-6002和低剂量的L-多巴还可以额外改善运动障碍，并增加运动能力。与D_1激动剂相比，L-多巴和喹比罗对KW-6002的抗帕金森病作用更为明显。然而，尽管产生了增强的抗帕金森反应，KW-6002并没有加剧L-多巴诱导的运动障碍，在MPTP治疗的普通绒猴中，先前因暴露于L-多巴而表现出运动障碍。选择性腺苷A(2A)受体拮抗剂，如KW-6002，可能是减少L多巴治疗帕金森病剂量的方法之一，并可能成为一种单独治疗或与多巴胺能药物联合治疗帕金森病的新方法。(C)2000年学术出版社。
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 Ha 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. (C) 2000 Academic Press.