Stocchi F, Bonamartini A, Vacca L, Ruggieri S
Department of Neurosciences, University of Rome La Sapienza, Italy.
Eur Neurol. 1996;36 Suppl 1:38-42. doi: 10.1159/000118882.
Fluctuations in motor performance and dyskinesias are a common problem in the long-term management of Parkinson's disease. The pharmacokinetics and the pharmacodynamics of levodopa, loss of presynaptic dopamine terminals, alterations in postsynaptic dopamine receptor sensitivity, or changes in the modulatory influences of nondopaminergic transmitter system could play a pathogenic role. The short half-life of levodopa and its absorption and transport are important factors. The pharmacodynamic response to levodopa changes during long-term therapy. An absolute threshold in plasma levodopa level, below which the patients are off, appears. The patients show a therapeutic window for levodopa which becomes narrower with time. This therapeutic window can be widened by giving continuous infusion of dopaminergic drugs. Motor fluctuations can be ameliorated by a more physiological continuous stimulation of the receptor site and by avoiding repeated shifting in levodopa levels. Long-term complications are attenuated by an early combination of levodopa with dopamine agonist.
运动功能波动和异动症是帕金森病长期管理中的常见问题。左旋多巴的药代动力学和药效学、突触前多巴胺能终末的丧失、突触后多巴胺受体敏感性的改变或非多巴胺能递质系统调节作用的变化可能起致病作用。左旋多巴的短半衰期及其吸收和转运是重要因素。长期治疗期间对左旋多巴的药效学反应会发生变化。血浆左旋多巴水平出现一个绝对阈值，低于该阈值患者就处于“关”期。患者对左旋多巴表现出一个治疗窗，且该治疗窗会随着时间变窄。通过持续输注多巴胺能药物可拓宽这个治疗窗。通过更生理性地持续刺激受体部位并避免左旋多巴水平的反复波动，可改善运动波动。通过早期将左旋多巴与多巴胺激动剂联合使用，可减轻长期并发症。
