Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Chem Biodivers. 2011 Jul;8(7):1189-204. doi: 10.1002/cbdv.201000269.
Alzheimer's disease (AD) is the fourth leading cause of death in adults, characterized by hallmark neuritic plaques and neurofibrillary tangles. Current treatments focus only on symptom relief. As a possible new treatment option for AD, huperzine A's chemistry, pharmacology, and clinical effectiveness are assessed. The chemical synthesis of huperzine A has been optimized, while an in vitro technique has provided a renewable plant source. Pharmacological studies showed that the drug inhibits the enzyme acetylcholinesterase reversibly and selectively. Huperzine A also displayed good pharmacokinetics with a rapid absorption and a wide distribution in the body at a low to moderate rate of elimination. Presently, inadequate toxicity data in human have been reported, yet animal studies demonstrated mild to moderate cholinergic side effects at therapeutic doses. Previous clinical trials have shown improvement in memory function using MMSE, MQ, ADAS-COG, and ADL tests. In an unpublished phase II clinical trial, the ADAS-COG and MMSE tests indicated cognitive enhancement at a dose of 0.4 mg, yet no improvement was observed at a dose of 0.2 mg. The MMSE scores indicated cognitive enhancement at 0.4 mg. Promising data suggested that huperzine A is well tolerated at doses up to 0.4 mg for 24 weeks. Therefore, huperzine A seems to be a potential treatment option for AD.
阿尔茨海默病（AD）是导致成年人死亡的第四大原因，其特征是存在标志性的神经纤维缠结和神经原纤维缠结。目前的治疗方法仅侧重于缓解症状。作为 AD 的一种可能的新治疗选择，对石杉碱甲的化学、药理学和临床疗效进行了评估。石杉碱甲的化学合成已经得到了优化，同时一种体外技术提供了可再生的植物来源。药理学研究表明，该药物可逆且选择性地抑制乙酰胆碱酯酶。石杉碱甲还表现出良好的药代动力学特性，吸收迅速，在体内分布广泛，消除率低至中等。目前，人类的毒性数据不足，但动物研究表明，在治疗剂量下会产生轻度至中度的胆碱能副作用。先前的临床试验表明，使用 MMSE、MQ、ADAS-COG 和 ADL 测试可以改善记忆功能。在一项未发表的 II 期临床试验中，ADAS-COG 和 MMSE 测试表明，在 0.4mg 剂量下认知能力增强，但在 0.2mg 剂量下没有观察到改善。MMSE 评分表明在 0.4mg 剂量下认知能力增强。有前途的数据表明，石杉碱甲在 24 周内的剂量高达 0.4mg 时耐受性良好。因此，石杉碱甲似乎是 AD 的一种潜在治疗选择。
