Spencer S E, Wooten G F
Neurology. 1984 Aug;34(8):1105-8. doi: 10.1212/wnl.34.8.1105.
Rats with unilateral lesions of the substantia nigra were treated with L-dopa 25 mg/kg subcutaneously 30 minutes after treatment with carbidopa 25 mg/kg intraperitoneally. In the ipsilateral striatum, dopamine levels achieved a peak of 1.57 +/- 0.63 micrograms/g (control 0.19 +/- 0.05 micrograms/g) at 20 minutes and did not differ from controls by 90 minutes after L-dopa administration. Dopamine levels peaked in the contralateral striatum at 45 minutes (11.96 +/- 0.14 micrograms/g, where control levels were 7.74 +/- 0.22 micrograms/g) and returned to control values by 180 minutes. These data suggest that in patients with advanced Parkinson's disease, L-dopa administration results in a smaller increase and a shorter duration of elevation in striatal dopamine concentration than in controls. These observations support the hypothesis that the "wearing-off" phenomenon that occurs during the treatment of patients with Parkinson's disease occurs as a consequence of a reduction in the rate of conversion of L-dopa to dopamine and perhaps diminished capacity for the storage of dopamine.
在用25mg/kg卡比多巴腹腔注射治疗30分钟后，对单侧黑质损伤的大鼠皮下注射25mg/kg左旋多巴。在同侧纹状体中，左旋多巴给药20分钟时多巴胺水平达到峰值1.57±0.63微克/克（对照组为0.19±0.05微克/克），给药90分钟后与对照组无差异。对侧纹状体中多巴胺水平在45分钟时达到峰值（11.96±0.14微克/克，对照组水平为7.74±0.22微克/克），并在180分钟时恢复到对照值。这些数据表明，在晚期帕金森病患者中，与对照组相比，给予左旋多巴后纹状体多巴胺浓度升高幅度较小且持续时间较短。这些观察结果支持这样的假说，即帕金森病患者治疗期间出现的“剂末现象”是由于左旋多巴向多巴胺的转化速率降低以及多巴胺储存能力可能降低所致。
