帕金森病合并运动波动和异动症患者的中枢左旋多巴流入及对左旋多巴的临床运动反应

Central levodopa influx and the clinical motor response to levodopa in patients with Parkinson disease complicated with motor fluctuations and dyskinesias.

作者信息

López-Ariztegui Nuria, Arévalo Maria Angeles, de Ceballos Maria L, Grandas Francisco

机构信息

Movement Disorders Research Unit, Hospital Universitario Gregorio Marañón, c/ Doctor Esquerdo 46, Madrid, Spain.

出版信息

Clin Neuropharmacol. 2009 Nov-Dec;32(6):321-5. doi: 10.1097/WNF.0b013e3181b40378.

DOI:10.1097/WNF.0b013e3181b40378

PMID:19667975

Abstract

OBJECTIVE

To study the possible relationship between central levodopa influx and short-term antiparkinsonian and dyskinetic responses to levodopa in patients with Parkinson disease.

METHODS

The clinical response to a single oral dose of standard and controlled-release levodopa/carbidopa was assessed in 12 patients with Parkinson disease complicated with motor fluctuations and dyskinesias. Plasma concentrations of levodopa and large neutral amino acids were determined, and the theoretical central levodopa influx was calculated using a model based on competitive inhibition of substrates to cross the blood-brain barrier.

RESULTS

The mean (SD) central levodopa influxes at the onset of the antiparkinsonian clinical effect were 19.7 (10.9 x 10(-3) and 19.1 (7.4 x 10(-3) nmol min(-1) g(-)1 (P >0.1) for standard and controlled-release levodopa, respectively. The mean (SD) central levodopa influxes at the onset of choreic dyskinesias were 20.1 (8.2 x 10 (-3) and 19.9 (10.8 x 10(-3) nmol min (-1) g(-)1 (P 9 0.1) for standard and controlled-release levodopa, respectively. During the tests, choreic dyskinesias were associated with a central levodopa influx of 10 x 10(-3) nmol min(-1) g(-1) or greater, and foot dystonia occurred with a central levodopa influx less than 9 x 10(-3) nmol min(-1) g(-1).

CONCLUSIONS

The clinical response to levodopa in patients with advanced Parkinson disease may be related to central levodopa influx. We found no differences in the central levodopa influx threshold for clinical improvement with different levodopa formulations. The central levodopa influxes at the onset of choreic dyskinesias and antiparkinsonian effect were similar. Choreic dyskinesias and foot dystonia were associated with high and low central levodopa influx, respectively.

摘要

目的

研究帕金森病患者中枢左旋多巴流入与左旋多巴短期抗帕金森病及异动症反应之间的可能关系。

方法

评估12例合并运动波动和异动症的帕金森病患者单次口服标准和控释左旋多巴/卡比多巴后的临床反应。测定左旋多巴和大中性氨基酸的血浆浓度，并使用基于底物竞争性抑制穿过血脑屏障的模型计算理论中枢左旋多巴流入量。

结果

标准和控释左旋多巴在抗帕金森病临床效应开始时的平均（标准差）中枢左旋多巴流入量分别为19.7（10.9×10⁻³）和19.1（7.4×10⁻³）nmol·min⁻¹·g⁻¹（P>0.1）。舞蹈样异动症开始时标准和控释左旋多巴的平均（标准差）中枢左旋多巴流入量分别为20.1（8.2×10⁻³）和19.9（10.8×10⁻³）nmol·min⁻¹·g⁻¹（P>0.1）。在测试期间，舞蹈样异动症与中枢左旋多巴流入量≥10×10⁻³ nmol·min⁻¹·g⁻¹相关，足肌张力障碍发生时中枢左旋多巴流入量<9×10⁻³ nmol·min⁻¹·g⁻¹。