Arnal F, Coté L J, Ginsburg S, Lawrence G D, Naini A, Sano M
Department of Neurology, College of Physicians & Surgeons, Columbia University, New York, N.Y. 10032.
Neurochem Res. 1990 Jun;15(6):587-91. doi: 10.1007/BF00973747.
We have synthesized the tertiary amines of pyridostigmine and neostigmine, 3-pyridinol dimethylcarbamate (norpyridostigmine) and 3-dimethylaminophenol dimethylcarbamate (norneostigmine) respectively, and we have tested their abilities to cross the blood-brain barrier and inhibit mouse brain AChE activity. The in vivo inhibition of AChE activity by norpyridostigmine reaches 72% at 10 minutes which is comparable to that seen with physostigmine (73% at 10 minutes). Inhibition by norneostigmine is less effective (50% at 10 minutes) and approaches that obtained with tetrahydroaminoacridine (57% at 10 minutes). These data show that both norpyridostigmine and norneostigmine cross the blood-brain barrier and that they are effective inhibitors of mouse brain AChE activity. These drugs could be useful in the treatment of memory impairment associated with Alzheimer's disease, and other memory disorders.
我们分别合成了吡啶斯的明和新斯的明的叔胺，即3-吡啶醇二甲基氨基甲酸酯（去甲吡啶斯的明）和3-二甲基氨基苯酚二甲基氨基甲酸酯（去甲新斯的明），并测试了它们穿越血脑屏障和抑制小鼠脑乙酰胆碱酯酶（AChE）活性的能力。去甲吡啶斯的明在体内对AChE活性的抑制在10分钟时达到72%，这与毒扁豆碱的抑制效果相当（10分钟时为73%）。去甲新斯的明的抑制效果较差（10分钟时为50%），接近四氢氨基吖啶的抑制效果（10分钟时为57%）。这些数据表明，去甲吡啶斯的明和去甲新斯的明都能穿越血脑屏障，并且它们是小鼠脑AChE活性的有效抑制剂。这些药物可能对治疗与阿尔茨海默病相关的记忆障碍以及其他记忆障碍有用。
