Bachurin S O
Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka, Moscow region, Russia.
Med Res Rev. 2003 Jan;23(1):48-88. doi: 10.1002/med.10026.
Alzheimer's disease (AD) is the most common form of dementia, which is characterised by progressive deterioration of memory and higher cortical functions that ultimately result in total degradation of intellectual and mental activities. Modern strategies in the search of new therapeutic approaches are based on the morphological and biochemical characteristics of AD, and focused on following directions: agents that compensate the hypofunction of cholinergic system, agents that interfere with the metabolism of beta-amyloid peptide, agents that protect nerve cells from toxic metabolites formed in neurodegenerative processes, agents that activate other neurotransmitter systems that indirectly compensate for the deficit of cholinergic functions, agents that affect the process of the formation of neurofibrillary tangles, anti-inflammatory agents that prevent the negative response of nerve cells to the pathological process. The goal of the present review is the validation and an analysis from the point of view of medicinal chemistry of the principles of the directed search of drugs for the treatment and prevention of AD and related neurodegenerative disorders. It is based on systematization of the data on biochemical and structural similarities in the interaction between physiologically active compounds and their biological targets related to the development of such pathologies. The main emphasis is on cholinomimetic, anti-amyloid and anti-metabolic agents, using the data that were published during the last 3 to 4 years, as well as the results of clinical trials presented on corresponding websites.
阿尔茨海默病（AD）是最常见的痴呆形式，其特征是记忆和高级皮质功能进行性衰退，最终导致智力和精神活动完全退化。寻找新治疗方法的现代策略基于AD的形态学和生化特征，并集中在以下方向：补偿胆碱能系统功能减退的药物、干扰β-淀粉样肽代谢的药物、保护神经细胞免受神经退行性过程中形成的有毒代谢产物影响的药物、激活其他神经递质系统以间接补偿胆碱能功能缺陷的药物、影响神经原纤维缠结形成过程的药物、防止神经细胞对病理过程产生负面反应的抗炎药物。本综述的目的是从药物化学的角度验证和分析用于治疗和预防AD及相关神经退行性疾病的定向药物搜索原则。它基于对生理活性化合物与其与此类病理发展相关的生物靶点相互作用中生化和结构相似性数据的系统化。主要重点是拟胆碱药、抗淀粉样蛋白药和抗代谢药，使用过去3至4年发表的数据以及相应网站上公布的临床试验结果。
