Shvaloff A, Neuman E, Guez D
Division Thérapeutique de Médécine Appliquée, Institut de Recherche Internationales Servier, Courbevoie, France.
Psychopharmacol Bull. 1996;32(3):343-52.
Therapeutic research is being stepped up to light Alzheimer's disease (AD), although its heterogeneity, the insufficiency of physiopathological knowledge, and the lack of a reference treatment impede the development of a drug to combat it. However, progress has opened up many avenues. Some recent approaches that have led to therapeutic research are identification of biochemical abnormalities, identification of dysfunction in several neurotransmitter systems (cholinergic, catecholaminergic, serotonergic, and peptidergic systems), and the study of senile plaques and neurofibrillary degeneration tangles. Although some types of therapy have been used for a long time (e.g., metabolic products such as nootropes), recently developed drugs target different systems: for example, neurotransmitter systems are important for symptomatic improvements in cognitive functions. The principal improvements expected with some new anticholinesterases whose role is to increase the available amount of central acetylcholine are in memory and attention. Second, retarding neuronal degeneration by acting on amyloid plaques is another possible future therapy. Here, protease inhibitors appear to be interesting tools. Third, the endototoxin etiology of neurodegenerative illnesses remains uncertain. After the first attempts with N-methyl-D-aspartate (NMDA) antagonists that had inescapable side effects, hopes rose with some new pharmacological tools such as the AMPA/kainate antagonists. Fourth, a possible stimulation of neuronal plasticity by neurotrophic factors such as nerve growth factor (NGF) constitutes another prospected research area. Fifth, the inflammatory aspects of degenerative diseases attract the attention of many laboratories and preliminary reports are hopeful. Finally, out of the established pharmacological tools, gene therapy, though still hypothetical, may become the expected treatment in the future. Pharmacotherapy used in the most common types of dementia has until now been largely palliative and dealt with symptoms. It is nonetheless not unreasonable to look forward to the development of drugs that will be able to combat the evolution of the dementia itself, rather than its symptoms. A list of different products developed to treat AD is concluded by an evaluation of the expected results and, in particular, the orientations likely to be necessary.
治疗阿尔茨海默病（AD）的研究正在加速推进，尽管其异质性、生理病理学知识的不足以及缺乏参考治疗方法阻碍了抗AD药物的研发。然而，研究进展开辟了许多途径。近期一些推动治疗研究的方法包括识别生化异常、确定几种神经递质系统（胆碱能、儿茶酚胺能、血清素能和肽能系统）的功能障碍，以及研究老年斑和神经原纤维变性缠结。尽管某些类型的治疗方法已经使用了很长时间（例如，益智药等代谢产物），但最近研发的药物针对不同系统：例如，神经递质系统对于认知功能的症状改善很重要。一些新型抗胆碱酯酶的主要预期改善作用是增加中枢乙酰胆碱的可用量，从而改善记忆和注意力。其次，通过作用于淀粉样斑块来延缓神经元变性是另一种可能的未来治疗方法。在此方面，蛋白酶抑制剂似乎是有前景的工具。第三，神经退行性疾病的内毒素病因仍不确定。在首次尝试使用有不可避免副作用的N-甲基-D-天冬氨酸（NMDA）拮抗剂后，一些新型药理学工具如AMPA/海人藻酸拮抗剂带来了新希望。第四，神经营养因子如神经生长因子（NGF）可能对神经元可塑性的刺激构成另一个预期的研究领域。第五，退行性疾病的炎症方面吸引了许多实验室的关注，初步报告令人期待。最后，在已有的药理学工具中，基因治疗虽然仍属假设，但可能成为未来预期的治疗方法。迄今为止，用于最常见类型痴呆症的药物治疗在很大程度上一直是姑息性的，只能处理症状。然而，期待开发出能够对抗痴呆症本身进展而非其症状的药物并非不合理。通过对预期结果，特别是可能需要的方向进行评估，得出了一份用于治疗AD的不同产品清单。
