Mode of action and mechanisms of resistance for antimalarial drugs.
Understanding the mode of action of and mechanism of resistance to drugs is central to optimising their use, and discovering new therapeutics with novel targets. We have limited understanding of how antimalarial drugs work and how resistance emerges. With few exceptions, antimalarial drugs in current use belong to a limited collection of chemical structures that act on a small number of partially characterised biochemical targets. Resistance has emerged to many of these compounds. The use of closely related compounds has promoted the spread of multidrug resistant parasites. This review intends to collate contemporary knowledge, and also to highlight conflicting views on unresolved issues.
Olliaro
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World Health Organization, Communicable Diseases Cluster (CDS), UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), CH-1211 27, Geneva, Switzerland. olliarop@who.ch
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins; D053626:Atovaquone; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005493:Folic Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use; D009154:Mutation; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use; D009696:Nucleic Acids / Q000037:antagonists & inhibitors; D010961:Plasmodium / Q000187:drug effects; D002727:Proguanil / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use
D000962:Antimalarials; D037621:Artemisinins; D005493:Folic Acid Antagonists; D007783:Lactones; D009285:Naphthoquinones; D009696:Nucleic Acids; D011804:Quinolines; D012717:Sesquiterpenes; D002727:Proguanil; C075875:artemisin; D053626:Atovaquone