Mouradian M M, Heuser I J, Baronti F, Chase T N
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892.
Ann Neurol. 1990 Jan;27(1):18-23. doi: 10.1002/ana.410270105.
The management of fluctuations in motor function complicating advanced Parkinson's disease with continuously administered dopaminomimetics was studied in 12 patients. In response to 7 to 12 days of round-the-clock intravenous infusions of levodopa, fluctuations in motor performance gradually diminished, ultimately by more than 40%. The beneficial effect persisted for about 6 days after withdrawal of continuous parenteral treatment and resumption of standard oral therapy. Clinical improvement was associated with changes in several pharmacological indices: Acute dose-response studies of intravenous levodopa showed a shift of the curve to the right in the immediate postinfusion phase compared to preinfusion studies; the therapeutic index improved significantly as patients demonstrated about 76% increased beneficial antiparkinsonian response with an equal degree of toxic dyskinetic effects; and the duration of action of levodopa was prolonged by 30%. These results suggest that changes in central dopaminergic mechanisms contributing to motor complications in advanced Parkinson's disease can be modified by procedures that provide continuous dopamine replacement. Presumably these modifications underlie the gradual amelioration of motor fluctuations over several days of round-the-clock therapy. Results of the present study also suggest potential deleterious effects of chronic intermittent oral treatment in the development of motor complications and thus support the role of long-term, continuous administration of dopaminomimetics.
对12例晚期帕金森病患者使用持续多巴胺能激动剂治疗时运动功能波动的管理进行了研究。在接受左旋多巴7至12天的全天候静脉输注后，运动表现的波动逐渐减少，最终减少超过40%。在停止持续胃肠外治疗并恢复标准口服治疗后，有益效果持续约6天。临床改善与几个药理学指标的变化相关：与输注前研究相比，静脉注射左旋多巴的急性剂量反应研究显示在输注后即刻阶段曲线向右移动；治疗指数显著改善，因为患者在同等程度的毒性运动障碍作用下，抗帕金森病有益反应增加约76%；左旋多巴的作用持续时间延长了30%。这些结果表明，通过提供持续多巴胺替代的程序，可以改变导致晚期帕金森病运动并发症的中枢多巴胺能机制。推测这些改变是全天候治疗数天内运动波动逐渐改善的基础。本研究结果还表明慢性间歇性口服治疗在运动并发症发生中的潜在有害作用，从而支持长期持续给予多巴胺能激动剂的作用。
