Rinne U K
J Neural Transm. 1981;51(1-2):161-74. doi: 10.1007/BF01664013.
Long-term follow-up of parkinsonian patients has shown that although levodopa treatment significantly improves the parkinsonian symptoms and the quality of life of parkinsonian patients for several years, various distressing difficulties arise during chronic levodopa treatment, such as the loss of benefit, dyskinesias, on-off phenomena, postural instability and dementia. Clinical, neuropsychological, mortality and post-mortem brain studies indicate that levodopa as a replacement therapy does not modify the progression of the underlying pathology and the natural course of the disease. It seems that levodopa has only a limited period of optimal usefulness in the treatment of Parkinson's disease. However, at present there is no better or more potent therapeutic agent available than levodopa and it is still the primary treatment of Parkinson's disease. It would be reasonable not to begin levodopa treatment in patients with mild symptoms but to withhold levodopa until the severity of symptoms really makes its use necessary. Thus it is possible to get the maximal long functional benefit. Post-mortem brain studies have shown that in Parkinson's disease there is not only a progressive loss of dopaminergic substantia nigra neurons but there are also significant changes in the striatal dopamine receptors. In some patients a denervation supersensitivity seems to develop and in some others a loss of dopamine receptors in the striatum. However, in advanced parkinsonian patients with a deteriorating response to levodopa, there seem to be still enough dopamine receptors in the striatum for drugs stimulating the dopamine receptors directly to improve the parkinsonian disability. Indeed, recent evidence indicates that dopaminergic agonists, such as bromocriptine, seem to be a significant and valuable adjuvant therapy to levodopa in parkinsonian patients with a deteriorating response and/or the on-off phenomena. Although bromocriptine is not completely satisfactory, it is a significant opening to a new mode of treatment. In the future it will be very important to develop more potent and selective dopaminergic agonists affecting only those striatal receptors which are mainly responsible for the parkinsonian symptoms. Then a better therapeutic response is likely to occur and many central side effects can be avoided. Current difficulties in the management of Parkinson's disease greatly depend on the fact that we are dealing with a symptomatic therapy. It is hoped that future research will soon lead to a discovery of the primary cause and consequently to a causal therapy of Parkinson's disease.
帕金森病患者的长期随访表明，尽管左旋多巴治疗在数年内能显著改善帕金森病症状及患者生活质量，但在长期左旋多巴治疗过程中会出现各种令人困扰的问题，如疗效丧失、运动障碍、开关现象、姿势不稳和痴呆等。临床、神经心理学、死亡率及尸检脑研究表明，左旋多巴作为替代疗法并不能改变潜在病理过程的进展及疾病的自然进程。似乎左旋多巴在治疗帕金森病方面仅有一段有限的最佳有效时期。然而，目前没有比左旋多巴更好或更有效的治疗药物，它仍是帕金森病的主要治疗方法。对于症状较轻的患者，合理的做法是暂不开始左旋多巴治疗，而是推迟使用，直到症状严重程度确实需要使用时再用。这样有可能获得最大的长期功能益处。尸检脑研究表明，在帕金森病中，不仅存在多巴胺能黑质神经元的渐进性丧失，纹状体多巴胺受体也有显著变化。在一些患者中似乎会出现去神经超敏反应，而在另一些患者中则是纹状体多巴胺受体丧失。然而，在对左旋多巴反应逐渐恶化的晚期帕金森病患者中，纹状体中似乎仍有足够的多巴胺受体，可供直接刺激多巴胺受体的药物改善帕金森病所致残疾。事实上，最近的证据表明，多巴胺能激动剂，如溴隐亭，对于反应逐渐恶化和/或出现开关现象的帕金森病患者，似乎是左旋多巴的一种重要且有价值的辅助治疗方法。尽管溴隐亭并不完全令人满意，但它为一种新的治疗模式带来了重要开端。未来，研发更有效且更具选择性的多巴胺能激动剂，使其仅作用于那些主要导致帕金森病症状的纹状体受体，将非常重要。届时可能会出现更好的治疗反应，并可避免许多中枢性副作用。目前帕金森病治疗中的困难很大程度上取决于我们所采用的是对症治疗这一事实。希望未来的研究能很快找到主要病因，从而实现帕金森病的病因治疗。
