Klockgether T, Löschmann P A, Wüllner U
University of Tübingen, Germany.
Curr Opin Neurol. 1994 Aug;7(4):346-52. doi: 10.1097/00019052-199408000-00012.
This article reviews new medical and surgical treatments for Parkinson's disease (PD). Catechol-O-methyl-transferase (COMT) inhibitors supplement the variety of antiparkinsonian drugs interacting with the dopaminergic system. Clinical studies show that COMT inhibitors prolong the action of levodopa in patients with the "wearing off" phenomenon. The atypical antipsychotic drug clozapine is the treatment of choice for the alleviation of levodopa-induced psychosis. Clozapine also has beneficial effects on tremor and levodopa-induced dyskinesias. Thus, COMT inhibitors and clozapine provide new opportunities for the treatment of patients with longstanding PD and fluctuating responses to levodopa. Experimental evidence in animals suggests that glutamate antagonists have symptomatic and neuroprotective actions in PD. At present, however, only weak antiglutamatergic drugs that have low specificity, such as memantine, amantadine, and budipine are available for clinical studies. Neurotrophic factors, in particular ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, are among the most promising new approaches for neuroprotection in PD. Problems of bioavailability, however, thus far preclude their use in patients. An improved understanding of the pathophysiology of parkinsonism has led to a renaissance of stereotaxic surgery. The subthalamic nucleus is a potential new target for surgical intervention. Ventroposterior pallidotomy has been shown to improve not only rigidity and tremor, but also akinesia. The techniques for thalamic interventions have been refined by introducing chronic thalamic stimulation. Future transplantation approaches to PD will focus on the use of genetically modified cells carrying genes for dopamine-synthesizing enzymes or neurotrophic factors. Animal studies show the feasibility of in vivo gene transfer for the treatment of PD.
本文综述了帕金森病（PD）的新型药物和手术治疗方法。儿茶酚-O-甲基转移酶（COMT）抑制剂丰富了与多巴胺能系统相互作用的抗帕金森病药物种类。临床研究表明，COMT抑制剂可延长左旋多巴在出现“剂末现象”患者中的作用时间。非典型抗精神病药物氯氮平是缓解左旋多巴所致精神病的首选治疗药物。氯氮平对震颤和左旋多巴所致异动症也有有益作用。因此，COMT抑制剂和氯氮平为长期患PD且对左旋多巴反应波动的患者提供了新的治疗机会。动物实验证据表明，谷氨酸拮抗剂在PD中具有对症和神经保护作用。然而，目前仅有美金刚、金刚烷胺和布地品等特异性较低的弱抗谷氨酸能药物可用于临床研究。神经营养因子，尤其是睫状神经营养因子和胶质细胞源性神经营养因子，是PD神经保护最有前景的新方法之一。然而，生物利用度问题至今仍阻碍其在患者中的应用。对帕金森病病理生理学的深入理解促使立体定向手术再度兴起。丘脑底核是手术干预的一个潜在新靶点。苍白球腹后内侧部毁损术已被证明不仅可改善强直和震颤，还可改善运动不能。通过引入慢性丘脑刺激，丘脑干预技术已得到改进。未来PD的移植治疗方法将集中于使用携带多巴胺合成酶基因或神经营养因子基因的基因修饰细胞。动物研究表明，体内基因转移治疗PD具有可行性。
