Ibach Bernd, Haen Ekkehard
Memory Disorders Clinic, Gerontopsychiatric and Clinical Pharmacology Research Unit, Department of Psychiatry, University of Regensburg, Bezirksklinikum Regensburg, Germany.
Curr Pharm Des. 2004;10(3):231-51. doi: 10.2174/1381612043386509.
Alzheimer's Disease (AD) is the most common cause for dementia in our ageing population, which leads to a slowly progressive, irretrievable ruination of mental function. The destructive, primarily degenerative condition is neuropathologically characterized by the formation of amyloid plaques, neurofibrillary tangles and loss of neurons and synapses as well. Research during the past twenty years revealed early in the disease course a degeneration of cholinergic nuclei localised in the basal forebrain. Impairment of this cholinergic system, which projects into large areas of the limbic system and the neocortex is followed by disturbance of attentional processes and cognitive decline. The link between the cholinergic dysfunction and cognitive impairment has focused large scientific efforts to understand the neurobiology of cognition and to develop therapeutic tools for the fight against Alzheimer's Disease. Acetylcholinesterase inhibitors are currently the best established treatment for this devastating disease. This review describes historical aspects and the vast range of use of cholinesterase inhibitors in traditional societies and industrial nations. Second, the rational basis will be outlined for their development as medication, the so-called cholinergic hypotheses of AD. Third, acetylcholinesterase inhibitors currently available for the treatment of AD will be reviewed. This includes donepezil, galanthamine and rivastigmine. Tacrine, the first acetylcholinesterase inhibitor who became available in 1993 as a treatment for AD, does not play an essential role anymore besides his historical value, because of its hepatotoxicity. Although acetylcholinesterase inhibitors are no cure, these drugs can delay the progress of mental deterioration, reduce neuropsychiatric symptoms and therefore represent a rational therapeutic approach to the treatment of Alzheimer's Disease.
阿尔茨海默病（AD）是老年人群中痴呆症最常见的病因，它会导致精神功能缓慢进展且无法挽回的破坏。这种具有破坏性的主要退行性疾病在神经病理学上的特征是淀粉样斑块的形成、神经原纤维缠结以及神经元和突触的丧失。过去二十年的研究表明，在疾病进程早期，位于基底前脑的胆碱能核团会发生退化。该胆碱能系统投射到边缘系统和新皮质的大片区域，其功能受损会导致注意力过程紊乱和认知能力下降。胆碱能功能障碍与认知障碍之间的联系促使人们投入大量科学努力来理解认知的神经生物学，并开发对抗阿尔茨海默病的治疗手段。乙酰胆碱酯酶抑制剂是目前针对这种毁灭性疾病最成熟的治疗方法。本综述描述了胆碱酯酶抑制剂在传统社会和工业国家的历史背景及广泛应用。其次，将概述其作为药物开发的理论基础，即所谓的AD胆碱能假说。第三，将对目前可用于治疗AD的乙酰胆碱酯酶抑制剂进行综述。这包括多奈哌齐、加兰他敏和卡巴拉汀。他克林是1993年作为AD治疗药物问世的首个乙酰胆碱酯酶抑制剂，由于其肝毒性，除了具有历史价值外，已不再发挥重要作用。尽管乙酰胆碱酯酶抑制剂无法治愈疾病，但这些药物可以延缓精神衰退的进程，减轻神经精神症状，因此是治疗阿尔茨海默病的一种合理治疗方法。
