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[精神药物开发的最新进展(3)——用于治疗帕金森病或正在针对患者或模型动物进行研究的抗帕金森病药物]

[Recent progress in development of psychotropic drugs (3)--Antiparkinsonian agents applied in the treatment of Parkinson's disease or are under investigation for patients or model animals].

作者信息

Nomoto M

机构信息

Department of Pharmacology, Faculty of Medicine, Kagoshima University, Japan.

出版信息

Nihon Shinkei Seishin Yakurigaku Zasshi. 1996 Aug;16(4):113-22.

PMID:8905800
Abstract

Tremor, akinesia, rigidity and postual instability are key signs of Parkinson's disease. The most important one is akinesia, which includes decreased spontaneous locomotor activity, slowness of movement, awkwardness and freezing. On the other hand, an electrical focal lesion in the brain, neurotoxin to dopaminergic neurons such as 6-hydroxydopamine (6-OHDA) or I-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), cholinomimetic tremorogenic agents such as oxotremorine or tremorine, monoamine depleting agents such as reserpine or tetrabenazine, or dopamine receptor antagonists such as haloperidol are applied to render animal parkinsonism. The estimation of locomotor activity can be done accurately in animal models. Tremor can be studied using the animals treated by cerebral focal lesion, neurotoxins or cholinomimetics. Skillfulness is hard to estimate in animals, however, it can be done in primates. Freezing appeared in patients with levodopa treatment over a long period. This is a specific motor sign in Parkinson's disease, and cannot be observed in animals. Supplementing dopamine by levodopa administration, retarding the metabolism of levodopa or dopamine by dopa decarboxylase inhibitor (DCI), monoamine oxidase inhibitor type B (MAO-B) inhibitor or catechol-O-methyltransferase (COMT) inhibitor, dopamine receptor agonists, anticholinergic agents, dopamine release enhancer/ uptake inhibitor, N-methyl-D-aspartate (NMDA) receptor antagonists, adenosine receptor antagonists, neurotrophic factors, GM1-ganglioside and nicotinic receptor agonists have been applied in the treatment of Parkinson's disease or are under investigation for patients. Agents to facilitate nerve growth or to inhibit the degeneration of nerves will be developed in the future.

摘要

震颤、运动不能、强直和姿势不稳是帕金森病的关键体征。其中最重要的是运动不能,包括自发运动活性降低、运动迟缓、动作笨拙和冻结现象。另一方面,通过在脑内制造局灶性损伤、使用对多巴胺能神经元有毒性的神经毒素(如6-羟基多巴胺(6-OHDA)或1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP))、拟胆碱震颤诱发剂(如氧化震颤素或震颤素)、单胺耗竭剂(如利血平或丁苯那嗪)或多巴胺受体拮抗剂(如氟哌啶醇)来使动物患上帕金森综合征。在动物模型中可以准确评估运动活性。使用经脑局灶性损伤、神经毒素或拟胆碱药处理的动物可以研究震颤。然而,在动物中很难评估动作技巧性,不过在灵长类动物中可以做到。长期接受左旋多巴治疗的患者会出现冻结现象。这是帕金森病的一种特殊运动体征,在动物中无法观察到。通过给予左旋多巴补充多巴胺、使用多巴脱羧酶抑制剂(DCI)、B型单胺氧化酶抑制剂(MAO-B)、儿茶酚-O-甲基转移酶(COMT)抑制剂、多巴胺受体激动剂、抗胆碱能药物、多巴胺释放增强剂/摄取抑制剂、N-甲基-D-天冬氨酸(NMDA)受体拮抗剂、腺苷受体拮抗剂、神经营养因子、GM1神经节苷脂和烟碱受体激动剂来治疗帕金森病,或者这些药物正在针对患者进行研究。未来将会研发促进神经生长或抑制神经退变的药物。

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