Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Toxins (Basel). 2018 Nov 23;10(12):491. doi: 10.3390/toxins10120491.
This article describes the discovery and use of the South American cinchona bark and its main therapeutic (and toxic) alkaloids, quinine and quinidine. Since the introduction of cinchona to Europe in the 17th century, it played a role in treating emperors and peasants and was central to colonialism and wars. Over those 400 years, the medical use of cinchona alkaloids has evolved from bark extracts to chemical synthesis and controlled clinical trials. At the present time, the use of quinine and quinidine has declined, to a large extent due to their toxicity. However, quinine is still being prescribed in resource-limited settings, in severe malaria, and in pregnant women, and quinidine made a limited comeback in the treatment of several cardiac and neurological syndromes. In addition, the article presents more recent studies which improved our understanding of cinchona alkaloids' pharmacology. The knowledge gained through these studies will hopefully lead to a wider use of these drugs in precision medicine and to design of new generation, safer quinine and quinidine derivatives.
本文描述了南美金鸡纳树皮及其主要治疗（和毒性）生物碱奎宁和奎尼丁的发现和应用。自 17 世纪金鸡纳引入欧洲以来，它在治疗帝王和平民方面发挥了作用，是殖民主义和战争的核心。在这 400 年中，金鸡纳生物碱的医学用途已经从树皮提取物发展到化学合成和对照临床试验。目前，奎宁和奎尼丁的使用已经减少，在很大程度上是由于它们的毒性。然而，奎宁仍在资源有限的环境中用于严重疟疾和孕妇，奎尼丁在治疗几种心脏和神经系统综合征方面也有限地复出。此外，本文还介绍了最近的研究，这些研究增进了我们对金鸡纳生物碱药理学的理解。通过这些研究获得的知识有望使这些药物在精准医学中得到更广泛的应用，并设计出新一代更安全的奎宁和奎尼丁衍生物。
