Muenter M D, Sharpless N S, Tyce G M, Darley F L
Mayo Clin Proc. 1977 Mar;52(3):163-74.
The clinical, biochemical, and pharmacologic responses to L-dopa were studied in 87 patients with Parkinson's disease. Eleven of the 87 patients had a long-duration response, 39 had a short-duration response, and 37 had a combination of both. Thirty-four of the 39 patients with short-duration response to L-dopa experienced a consistent and reproducible sequence of clinical and biochemical events after each dose, characterized by improvement of parkinsonism and a single phase of dystonia occurring during or shortly after the peak of dopa concentration in plasma and during maximal clinical improvement. We have called this the I-D-I- response, for Parkinsonism-Improvement-Dystonia-Improvement-Parkinsonism. The remaining five patients all had the onset of the disease at an unusually young age and showed a distinctly different response pattern consisting of a first phase of dystonia, before there was any improvement, followed by a phase of improvement without dystonia and then by a second phase of dystonia before the abrupt return of parkinsonism. We have called this the D-I-D response, for Parkinsonism-Dystonia-Improvement-Dystonia-Parkinsonsim. Dystonia occurs in the D-I-D- response when the concentration of dopa in plasma passes through a critical but relatively low level, whereas it remains absent as long as the concentration of dopa remains above that level. In the I-D-I- response, dystonia is avoided by keeping the plasma concentration of dopa low, in the D-I-D- response by keeping it high. It is postulated that in the D-I-D response postsynaptic depolarization blockade due to supramaximal stimulation of the neuronal system mediating dystonia occurs, whereas in the I-D-I response the postsynaptic members of the same neuronal population respond with excitation but not with depolarization blockade.
对87例帕金森病患者的左旋多巴临床、生化及药理反应进行了研究。87例患者中,11例有长期反应,39例有短期反应,37例兼具两者。39例对左旋多巴有短期反应的患者中,34例在每次服药后出现了一致且可重复的临床和生化事件序列,其特征为帕金森症状改善,且在血浆多巴浓度峰值期间或之后不久以及临床最大改善期出现单一阶段的肌张力障碍。我们将此称为I-D-I反应,即帕金森症状-改善-肌张力障碍-改善-帕金森症状。其余5例患者均在异常年轻时发病,表现出明显不同的反应模式,包括在任何改善之前的第一阶段肌张力障碍,随后是无肌张力障碍的改善阶段,然后在帕金森症状突然复发之前出现第二阶段肌张力障碍。我们将此称为D-I-D反应,即帕金森症状-肌张力障碍-改善-肌张力障碍-帕金森症状。在D-I-D反应中,当血浆中多巴浓度经过一个临界但相对较低的水平时会出现肌张力障碍,而只要多巴浓度保持在该水平以上则不会出现。在I-D-I反应中,通过保持血浆多巴浓度较低来避免肌张力障碍,在D-I-D反应中则通过保持其较高来避免。据推测,在D-I-D反应中,由于介导肌张力障碍的神经元系统受到超强刺激,会发生突触后去极化阻滞,而在I-D-I反应中,同一神经元群体的突触后成员以兴奋反应,但不会出现去极化阻滞。