Tedroff J, Pedersen M, Aquilonius S M, Hartvig P, Jacobsson G, Långström B
Department of Neurology, University Hospital, Uppsala, Sweden.
Neurology. 1996 May;46(5):1430-6. doi: 10.1212/wnl.46.5.1430.
Changes in striatal binding of [11C]raclopride, a dopamine D2 receptor antagonist, induced by acute levodopa administration, were evaluated with PET in 10 patients with idiopathic Parkinson's disease (PD). The patients were scanned on two occasions: drug-free and 15 minutes after a 5-minute intravenous infusion of 3 mg/kg levodopa. Levodopa administration produced reductions in striatal [11C]raclopride uptake index with a rostrocaudal gradient. The most pronounced reduction was found in the posterior putamen (to 82% of baseline), followed by the anterior putamen (to 88% of baseline) and the caudate nucleus (to 94% of baseline). The magnitude of [11C]raclopride uptake index reduction correlated with drug-free disability. Moreover, in four hemiparkinsonian patients, a reduction in [11C]raclopride uptake index was measured in the putamen contralateral to the parkinsonian symptoms. The present results demonstrate a positive correlation between striatal dopaminergic nerve-terminal deficiency and the capacity for levodopa to increase synaptic dopamine and displace [11C]raclopride binding, which corresponds to an accelerated amine turnover in dopamine-depleted striatal tissue. We therefore suggest that dopaminergic degeneration in PD is paralleled by a progressive acceleration of amine turnover. This mechanistic consequence of nigrostriatal degeneration, the selective restoration of synaptic dopaminergic neurotransmission in denervated striatal subregions, may explain the effectiveness of levodopa in producing symptomatic benefits in early PD. However, we also suggest that in the vastly denervated striatum, as in advanced PD, an excessive acceleration of amine turnover results in swings in levodopa-induced synaptic dopamine levels that are far beyond normal. This phenomenon most likely plays a key role in the pathogenesis underlying the development of motor-response complications in PD.
采用正电子发射断层扫描（PET）技术，对10例特发性帕金森病（PD）患者急性给予左旋多巴后，多巴胺D2受体拮抗剂[11C]雷氯必利纹状体结合的变化进行了评估。患者在两个时间点进行扫描：一次是未用药时，另一次是在静脉注射3mg/kg左旋多巴5分钟后15分钟。给予左旋多巴后，纹状体[11C]雷氯必利摄取指数降低，呈现出从前向后的梯度变化。在后壳核发现最明显的降低（降至基线的82%），其次是前壳核（降至基线的88%）和尾状核（降至基线的94%）。[11C]雷氯必利摄取指数降低的幅度与未用药时的残疾程度相关。此外，在4例偏侧帕金森病患者中，对侧壳核的[11C]雷氯必利摄取指数也降低。目前的结果表明，纹状体多巴胺能神经末梢缺乏与左旋多巴增加突触多巴胺和取代[11C]雷氯必利结合的能力之间存在正相关，这对应于多巴胺耗竭的纹状体组织中胺周转的加速。因此，我们认为帕金森病中的多巴胺能变性与胺周转的逐渐加速平行。黑质纹状体变性的这一机制后果，即在去神经支配的纹状体亚区域中突触多巴胺能神经传递的选择性恢复，可能解释了左旋多巴在早期帕金森病中产生症状性益处的有效性。然而，我们也认为，在如晚期帕金森病中那样去神经支配严重的纹状体中，胺周转的过度加速导致左旋多巴诱导的突触多巴胺水平的波动远远超过正常水平。这种现象很可能在帕金森病运动反应并发症发生的发病机制中起关键作用。
