东莨菪碱的中枢药理机制研究进展
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四川大学生物治疗国家重点实验室

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国家重点研究发展计划


Advances in The Central Pharmacological Mechanism of Scopolamine
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State Key Laboratory of Biotherapy, Sichuan University

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National key research and development program

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    摘要:

    东莨菪碱(Scopolamine)是一种天然莨菪烷生物碱,于1880年从东莨菪中分离纯化,是最早发现的竞争性胆碱能受体拮抗剂之一。相比于阿托品等同类药物,东莨菪碱对血脑屏障的通透性更强,且在中枢神经系统中可长期滞留并发挥药理作用。东莨菪碱对中枢神经系统的作用被广泛用于晕动症、麻醉镇痛等,并在抑郁症等疾病中有广阔的应用前景。另一方面,东莨菪碱在一定剂量下会损伤认知、学习记忆和注意力等中枢神经系统功能,限制其临床用药。东莨菪碱的中枢神经系统毒性亦被广泛应用于健忘症和谵妄等动物模型研究,成为研究中枢胆碱能系统的重要工具。本文梳理了东莨菪碱的化学结构与分类,总结了其在中枢神经系统中的临床用药与毒性,讨论了其在胆碱能功能研究和临床前研究中的应用,以及中枢神经系统毒性所引发的争议,并针对东莨菪碱在中枢系统疾病的应用前景做了展望。

    Abstract:

    Scopolamine, a natural tropane alkaloid, was isolated in 1880 from Scopolia japonica and is considered one of the earliest competitive cholinergic receptor antagonists discovered. Compared to other drugs with similar effects such as atropine, scopolamine exhibits greater permeability across the blood-brain barrier and can remain in the central nervous system longer to exert pharmacological effects. The effects of scopolamine on the central nervous system are widely utilized in the treatment of motion sickness, anesthesia, and pain relief, and may be broadly applied to diseases such as depression. On the other hand, scopolamine can impair central nervous system functions such as cognition, learning and memory, and attention, which limits its clinical use. Additionally, the neurotoxicity of scopolamine has been widely used in animal models of amnesia and delirium and has become an important tool for studying the central cholinergic system. This article outlines the chemical structure and classification of scopolamine, summarizes its clinical use and toxicity in the central nervous system, discusses its application in cholinergic function research and preclinical studies, as well as the controversy surrounding its central nervous system toxicity. We also provided an outlook for the potential use of scopolamine in central nervous system diseases.

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  • 收稿日期:2023-03-17
  • 最后修改日期:2023-04-17
  • 录用日期:2023-08-09
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