Baas H, Harder S, Demisch L, Bürklin F, Stecker K, Fischer P A
Department of Neurology, University of Frankfurt/M., Federal Republic of Germany.
J Neural Transm Suppl. 1995;46:367-79.
The pathogenetic mechanisms which are responsible for the clinical manifestation of motor-fluctuations are poorly understood. Peripheral pharmacokinetics do obviously not play a significant role. For a better understanding of fluctuations exact knowledge and precise characterization of the levodopa induced motor-response (MR) might be useful. In a number of studies it has been demonstrated that this MR follows the "all or none" rule after a levodopa threshold concentration has been exceeded. Such a threshold is considered to exist in the plasma-compartiment as well as in the cerebral effect-compartiment. The specific character of the MR can be modified by the coadministration of dopamine-agonists. Dopamine-agonists lower the levodopa threshold and they reduce the time-lag between levodopa plasmaconcentration and MR. The duration of the MR can be prolonged but the intensity (amplitude) of the MR cannot be augmented. Most of these data to levodopa pharmacodynamics can be explained by a model which is presented in this paper and which is mainly based on cerebral pharmacokinetic mechanisms.
导致运动波动临床表现的发病机制目前仍知之甚少。外周药代动力学显然并未发挥重要作用。为了更好地理解波动情况，准确了解左旋多巴诱导的运动反应（MR）并进行精确表征可能会有所帮助。在多项研究中已证明，超过左旋多巴阈值浓度后，这种MR遵循“全或无”规则。人们认为在血浆隔室以及脑效应隔室中都存在这样一个阈值。多巴胺激动剂的联合使用可改变MR的特异性。多巴胺激动剂可降低左旋多巴阈值，并减少左旋多巴血浆浓度与MR之间的时间延迟。MR的持续时间可以延长，但MR的强度（幅度）无法增强。这些关于左旋多巴药效学的大多数数据都可以用本文提出的一个模型来解释，该模型主要基于脑药代动力学机制。
