Svensson A L, Nordberg A
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital B84, Sweden.
Neuroreport. 1998 May 11;9(7):1519-22. doi: 10.1097/00001756-199805110-00050.
The effect of the cholinesterase inhibitors tacrine and donepezil on A beta(25-35)-induced toxicity was investigated in rat pheochromocytoma PC12 cells by measuring the mitochondrial activity. Tacrine and donepezil was found in clinical relevant concentrations (10(-7)-10(-6) M) to attenuate A beta(25-35)-induced toxicity in PC12 cells. The neuroprotective effect of tacrine was blocked in the presence of the nicotinic antagonists mecamylamine (10(-5) M) and tubocurarine (10(-5) M), suggesting an interaction via nicotinic receptors. This study demonstrates that tacrine and donepezil can exert neuroprotective properties which might be of importance and contribute to the clinical efficacy of cholinesterase inhibitors in the treatment of Alzheimer's disease.
通过测量线粒体活性，研究了胆碱酯酶抑制剂他克林和多奈哌齐对大鼠嗜铬细胞瘤PC12细胞中β淀粉样蛋白（25-35）诱导毒性的影响。发现他克林和多奈哌齐在临床相关浓度（10^-7 - 10^-6 M）下可减轻PC12细胞中β淀粉样蛋白（25-35）诱导的毒性。在存在烟碱拮抗剂美加明（10^-5 M）和筒箭毒碱（10^-5 M）的情况下，他克林的神经保护作用被阻断，表明通过烟碱受体发生相互作用。本研究表明，他克林和多奈哌齐可发挥神经保护特性，这可能具有重要意义，并有助于胆碱酯酶抑制剂在治疗阿尔茨海默病中的临床疗效。
