Cinchona Alkaloids: Quinine and Quinidine

Psychiatric effects of malaria and anti-malarial drugs: historical and modern perspectives

“…The earliest human experience with the quinolines dates to discovery of the naturally-occurring drug quinine, a 4-quinolinemethanol alkaloid first isolated from the bark of the Cinchona tree in the seventeenth century, together with the related cinchona alkaloid quinidine [ 109 ]. Although reports from the early twentieth century noted that quinine could have significant psychiatric effects [ 11 ], including causing depression, mania, irritability and personality change [ 110 ], and that these might not be distinguished from those attributed to disease [ 7 ], only relatively recently has it become clear that quinine, independent of malaria infection, may cause a serious toxic state marked by symptoms including delirium and confusion [ 111 , 112 ].…”

Antimalarial Efficacy of Hydroxyethylapoquinine (SN-119) and Its Derivatives

“…Presently, quinine or quinidine is still widely used for treating severe malaria because of the lack of availability of intravenous artesunate (7)(8)(9). Periodic reports of drug resistance to quinine do exist, mainly in Southeast Asia and South America, but the development of resistance is slow and not sustained, classified as "low grade," with no "high-grade" resistance being noted for severe malaria cases (7).…”

“…Periodic reports of drug resistance to quinine do exist, mainly in Southeast Asia and South America, but the development of resistance is slow and not sustained, classified as "low grade," with no "high-grade" resistance being noted for severe malaria cases (7). In many cases, quinine treatment failure is due to noncompliance to a treatment regimen rather than an actual increase in the 50% inhibitory concentration (IC 50 ) (8,10).…”

“…In particular, higher doses of quinine and quinidine may result in cardiotoxicity associated with delayed ventricular depolarization and, in the case of quinidine, repolarization, leading to prolonged QRS and QT intervals, respectively (11). Blindness is another severe adverse event associated with quinine overdose, while other side effects include tinnitus, hearing loss, headache, and loss of taste sensation (8). In light of these quinineassociated toxicities, a novel compound, similar to quinine but less toxic, would be ideal as either a partner drug with artemisininrelated compounds or a replacement for other antimalarial drugs that have become ineffective due to resistance.…”

A highly contiguous, scaffold-level nuclear genome assembly for the Fever tree (Cinchona pubescens Vahl) as a novel resource for research in the Rubiaceae

“…Nevertheless, among them, C. pubescens or red Cinchona bark is now widely cultivated throughout the New and Old-World tropics, with some instances where the species has escaped cultivation and become invasive [14]. Extensive research on the structure, abundance, and chemical composition of quinine alkaloids in the Cinchona genus have been conducted [15], revealing further potential in novel drug discovery. However, the identity of the genes involved in the synthetic pathway of quinine alkaloids remain elusive.…”