Can we teach an old drug new tricks?

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• 作者：Jun-Hong Ch&rsquo ; ng¹ ; ^{chngjunhong@hotmail.com} ; Laurent Renia² ; Francois Nosten³ ; ⁴ ; Kevin S.W. Tan¹ ; ^{mictank@nus.edu.sg}
• 关键词：malaria ; Plasmodium falciparum ; chloroquine ; lysosomotropic ; drug resistance ; programmed cell death ; apoptosis ; digestive vacuole ; regimen ; dosage ; high dose ; dose escalation
• 刊名：Trends in Parasitology
• 出版年：2012
• 出版时间：June, 2012
• 年：2012
• 卷：28
• 期：6
• 页码：220-224
• 全文大小：210 K

文摘

Although resistance to chloroquine (CQ) has relegated it from modern chemotherapeutic strategies to treat Plasmodium falciparum malaria, new evidence suggests that higher doses of the drug may exert a different killing mechanism and offers this drug a new lease of life. Whereas the established antimalarial mechanisms of CQ are usually associated with nanomolar levels of the drug, micromolar levels of CQ trigger a distinct cell death pathway involving the permeabilization of the digestive vacuole of the parasite and a release of hydrolytic enzymes. In this paper, we propose that this pathway is a promising antimalarial strategy and suggest that revising the CQ treatment regimen may elevate blood drug levels to trigger this pathway without increasing the incidence of adverse reactions.