Rinne U K
Gerontology. 1982;28 Suppl 1:35-52. doi: 10.1159/000212572.
Parkinson's disease ranks among the most prevalent neurological diseases in the elderly. The disease usually begins after the age of 50 years, and the risk of the disease rises steeply with advancing age. The primary etiology of Parkinson's disease is still unknown, although the aging process may be an important predisposing factor. There is some overlapping between Parkinson's disease and senile dementia of Alzheimer's type, although both seem to be disease entities. In Parkinson's disease, the most prominent and significant neuropathological change is the progressive loss of substantia nigra dopamine neurons. Studied of striatal dopamine receptors showed that the specific binding of 3H-spiroperidol was either significantly increased or reduced in the caudate nucleus and putamen of parkinsonian patients without levodopa therapy. Scatchard analysis showed that there were corresponding changes in the number of receptors, but no significant changes in the mean dissociation constant. Increased binding of 3H-spiroperidol in the basal ganglia was also found in parkinsonian patients suffering from psychotic episodes and treated with neuroleptic drugs. Normal and low binding of 3H-spiroperidol was found in patients treated with levodopa. The behavior of dopamine receptors in the nucleus accumbens was similar to that of dopamine receptors in the striatum. Clinically, the patients with low binding of 3H-spiroperidol in the striatum were more disabled and had lost the beneficial response to levodopa. Thus in some patients with Parkinson's disease a denervation supersensitivity seemed to develop and in others a loss of postsynaptic dopamine receptor sites in the neostriatum. The latter alteration may contribute to the decreased response of parkinsonian patients to long-term levodopa therapy. However, in patients with a deteriorating response to levodopa, there seem to be still enough dopamine receptors in the striatum for drugs stimulating the dopamine receptors to alleviate directly the parkinsonian disability. Indeed, dopaminergic agonists seem to be a significant and valuable adjuvant therapy to levodopa for parkinsonian patients with a deteriorating response and/or on-off phenomena.
帕金森病是老年人中最常见的神经疾病之一。该病通常在50岁以后发病，且发病风险会随着年龄的增长而急剧上升。尽管衰老过程可能是一个重要的诱发因素，但帕金森病的主要病因仍然不明。帕金森病与阿尔茨海默型老年痴呆症之间存在一些重叠，不过两者似乎都是独立的疾病实体。在帕金森病中，最突出且显著的神经病理学变化是黑质多巴胺能神经元的逐渐丧失。对纹状体多巴胺受体的研究表明，在未接受左旋多巴治疗的帕金森病患者的尾状核和壳核中，3H-螺哌啶醇的特异性结合要么显著增加，要么减少。Scatchard分析显示受体数量有相应变化，但平均解离常数无显著变化。在患有精神症状并接受抗精神病药物治疗的帕金森病患者中，也发现其基底神经节中3H-螺哌啶醇的结合增加。接受左旋多巴治疗的患者中发现3H-螺哌啶醇的结合正常或降低。伏隔核中多巴胺受体的行为与纹状体中多巴胺受体的行为相似。临床上，纹状体中3H-螺哌啶醇结合较低的患者残疾程度更高，且对左旋多巴失去了有益反应。因此，在一些帕金森病患者中似乎会出现去神经超敏反应，而在另一些患者中则会出现新纹状体中突触后多巴胺受体位点的丧失。后一种改变可能导致帕金森病患者对长期左旋多巴治疗的反应降低。然而，对于对左旋多巴反应恶化的患者，纹状体中似乎仍有足够的多巴胺受体，使得刺激多巴胺受体的药物能够直接减轻帕金森病的残疾症状。事实上，对于反应恶化和/或出现开关现象的帕金森病患者，多巴胺能激动剂似乎是左旋多巴的一种重要且有价值的辅助治疗方法。
