Abstract
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.
Highlights
From Bark to Chemical SynthesisIn Protestant England, the support of the Vatican worked against the acceptance of the bark due to fears of popish plots [1,5,8]
Introduction of Cinchona Alkaloids as AntiarrhythmicAgentsThe effect of quinidine on cardiac function was first reported in 1914 by Wenckebach [27], who was aware of quinine use for more than 60 years before his studies
Walter Frey, in 1918, conducted the first systematic study on the effect of cinchona alkaloids in patients with atrial fibrillation and found that quinidine was more effective than quinine in cardioverting to sinus rhythm [29]
Summary
In Protestant England, the support of the Vatican worked against the acceptance of the bark due to fears of popish plots [1,5,8] It was the English apothecarian Robert Talbor who provoked public awareness of cinchona, in the late 17th century. Robert Talbor exploited the fears of the public and used cinchona as a secret remedy, not disclosing that the central ingredient was the Peruvian bark. He successfully treated the King of England Charles II and the young son of Louis XIV using the mysterious powder [1,8]. In 2007, Robert Williams repeated Rabe’s reaction under 1944 conditions and obtained quinine, thereby demonstrating that the total synthesis of quinine by Woodward-Doering and Rabe-Kindler was possible [16]
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