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石杉碱甲的精神药理学:一种对治疗阿尔茨海默病具有认知增强和神经保护特性的生物碱。

The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease.

作者信息

Zangara Andrea

机构信息

Cognitive Drug Research, CDR House, 24 Portman Road, Reading RG30 1EA, UK.

出版信息

Pharmacol Biochem Behav. 2003 Jun;75(3):675-86. doi: 10.1016/s0091-3057(03)00111-4.

DOI:10.1016/s0091-3057(03)00111-4
PMID:12895686
Abstract

Huperzine A (HupA), extracted from a club moss (Huperzia serrata), is a sesquiterpene alkaloid and a powerful and reversible inhibitor of acetylcholinesterase (AChE). It has been used in China for centuries for the treatment of swelling, fever and blood disorders. It has demonstrated both memory enhancement in animal and clinical trials and neuroprotective effects. Recently it has undergone double-blind, placebo-controlled clinical trials in patients with Alzheimer's disease (AD), with significant improvements both to cognitive function and the quality of life. Most of the clinical trials are from China, but HupA and derivatives are attracting considerable interest in the West, where AD is a major and growing concern. Furthermore, both animal and human safety evaluations have demonstrated that HupA is devoid of unexpected toxicity. Other interesting aspects of HupA pharmacological profile relate to its neuroprotective properties: it has been shown in animal studies that HupA can be used as a protective agent against organophosphate (OP) intoxication and that it reduces glutamate-induced cell death.

摘要

石杉碱甲(HupA)是从蛇足石杉中提取的一种倍半萜生物碱,是一种强效且可逆的乙酰胆碱酯酶(AChE)抑制剂。几个世纪以来,它在中国一直被用于治疗肿胀、发热和血液疾病。在动物试验和临床试验中,它都显示出具有增强记忆和神经保护作用。最近,它在阿尔茨海默病(AD)患者中进行了双盲、安慰剂对照临床试验,对认知功能和生活质量均有显著改善。大多数临床试验来自中国,但石杉碱甲及其衍生物在西方引起了相当大的关注,在西方,AD是一个主要且日益受到关注的问题。此外,动物和人体安全性评估均表明石杉碱甲没有意外毒性。石杉碱甲药理学特性的其他有趣方面涉及其神经保护特性:动物研究表明,石杉碱甲可用作抗有机磷(OP)中毒的保护剂,并且它能减少谷氨酸诱导的细胞死亡。

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