Effect of coadministration of glutamate receptor antagonists and dopaminergic agonists on locomotion in monoamine-depleted rats.

M Gossel, W J Schmidt, W Löscher, W Zajaczkowski, W Danysz
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引用次数: 33

Abstract

Combinations of dopaminergic agonists with glutamate receptor antagonists have been suggested to be a possible alternative treatment of Parkinson's disease. To gain further insights into this possibility, the antagonist of the competitive AMPA-type glutamate receptor NBQX and the ion-channel blocker of the NMDA glutamate receptor (+)-MK-801 in combination with the dopamine D1 receptor agonists: SKF 38393, SKF 82958 and dihydrexidine; the dopamine D2 receptor agonist bromocriptine and the dopamine-precursor L-DOPA were tested in rats pretreated with reserpine and alpha-methyl-p-tyrosine. MK-801 on its own induced locomotor behaviour and potentiated the antiakinetic effects of dihydrexidine and L-DOPA but not of the other dopamine agonists tested. NBQX neither on its own nor coadministered with the dopamine agonists tested had an antiakinetic effect. These results indicate that agents, blocking the ion-channel of the NMDA receptor, might be useful adjuvants to some but not all dopaminomimetics in therapy of Parkinson's disease. The same does not seem to be true for the AMPA-antagonist NBQX.

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谷氨酸受体拮抗剂和多巴胺能激动剂对单胺衰竭大鼠运动的影响。
多巴胺能激动剂联合谷氨酸受体拮抗剂已被认为是帕金森病的一种可能的替代治疗方法。为了进一步了解这种可能性,研究人员将竞争性ampa型谷氨酸受体NBQX拮抗剂和NMDA型谷氨酸受体(+)-MK-801离子通道阻滞剂与多巴胺D1受体激动剂SKF 38393、SKF 82958和二氢西啶联合使用;多巴胺D2受体激动剂溴隐亭和多巴胺前体左旋多巴在利血平和α -甲基-对酪氨酸预处理的大鼠中进行检测。MK-801本身诱导运动行为并增强了二氢氧定和左旋多巴的抗运动作用,但对其他多巴胺激动剂没有作用。NBQX无论是单独使用还是与多巴胺激动剂联合使用都没有抗动力学作用。这些结果表明,阻断NMDA受体离子通道的药物可能是治疗帕金森病的一些有用的辅助剂,但不是所有的多巴胺模拟药物。ampa拮抗剂NBQX似乎并非如此。
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