Hauser R A, Zesiewicz T A
Department of Neurology, Tampa General Hospital, Florida, USA.
Med Clin North Am. 1999 Mar;83(2):393-414, vi. doi: 10.1016/s0025-7125(05)70111-5.
The two major questions in the treatment of early PD are (1) Does selegiline slow neuronal loss and delay the progression of clinical disability? and (2) Should dopamine agonists be used as initial symptomatic therapy in early disease rather than levodopa/PDI to reduce long-term disability and delay the onset of motor fluctuations and dyskinesia? Selegiline affords neuroprotection for dopamine neurons in cell culture systems and the results of several clinical trials are consistent with the hypothesis that it is neuroprotective in Parkinson's disease. Several clinical trials have found that initial symptomatic therapy with dopamine agonist to which levodopa/carbidopa is later added when needed leads to a lower incidence of long-term motor complications. These strategies are now being tested in prospective, randomized, blinded trials, many of which include PET or SPECT scans to assess the rate of dopamine neuron loss. These trials will provide more definitive answers to guide the early medial management of Parkinson's disease in the future.
(1)司来吉兰是否能减缓神经元丢失并延缓临床残疾的进展?(2)在疾病早期,多巴胺激动剂是否应作为初始症状性治疗药物,而非左旋多巴/外周多巴脱羧酶抑制剂,以减少长期残疾并延缓运动波动和异动症的发生?在细胞培养系统中,司来吉兰对多巴胺能神经元具有神经保护作用,多项临床试验结果与该药物在帕金森病中具有神经保护作用的假说一致。多项临床试验发现,以多巴胺激动剂作为初始症状性治疗,必要时再添加左旋多巴/卡比多巴,会使长期运动并发症的发生率更低。目前,这些策略正在前瞻性、随机、双盲试验中进行测试,其中许多试验包括PET或SPECT扫描,以评估多巴胺能神经元丢失的速率。这些试验将为未来指导帕金森病的早期内科治疗提供更明确的答案。