The Fever Tree: from Malaria to Neurological Diseases.

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.