[Mechanism of action of antimalarials. Value of combined atovaquone/proguanil].
Determining the mode of action of different antimalarial drugs at the cellular level is essential to optimizing their use and to understanding the mechanisms underlying plasmodial resistance. The main targets for antimalarial drugs in Plasmodium falciparum have been the food vacuole and mitochondrial system. A new target is recently discovered organelle named the apicoplast. The apicoplast is the site of a number of metabolic pathways crucial to the survival of the parasite. It may also be involved in DNA replication and transcription. Antimalarial drugs are classified into three groups according to site of action, i.e., drugs that act on the food vacuole, drugs that block metabolic synthesis and oxidative processes, and drugs that interfere with membrane processes. Knowledge of these sites of action has enabled identification of new drugs with the most promising potential for development. Current antimalarial strategies prioritize combination therapies such as atovaquone/proguanil or artemether/lumefantrine and prolonged treatments to limit the risk of inducing drug resistant Plasmodium.
Touze
J E
JE
Institut de Médecine Tropicale du Service de Santé des Armées, BP 46, Le Pharo, 13998, Marseille Armées, France. jetouze@aol.com
Fourcade
L
L
Pradines
B
B
Hovette
P
P
Paule
P
P
Heno
Ph
P
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000494:pharmacology*; D053626:Atovaquone; D004261:DNA Replication / Q000187:drug effects; D016054:DNA, Protozoan; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000494:pharmacology*; D015388:Organelles / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000472:pathogenicity; D002727:Proguanil / Q000008:administration & dosage* / Q000494:pharmacology*
D000962:Antimalarials; D016054:DNA, Protozoan; D009285:Naphthoquinones; D002727:Proguanil; D053626:Atovaquone