Chloroquine-Resistant Plasmodium falciparum: Effect of Substrate on Chloroquine and Amodiaquin Accumulation

  title={Chloroquine-Resistant Plasmodium falciparum: Effect of Substrate on Chloroquine and Amodiaquin Accumulation},
  author={Coy D. Fitch and Rekha Chevli and Yolanda Gonz{\'a}lez},
  journal={Antimicrobial Agents and Chemotherapy},
  pages={757 - 762}
Glucose stimulates the high-affinity processes of chloroquine and amodiaquin accumulation in owl monkey erythrocytes infected with a chloroquine-susceptible strain of Plasmodium falciparum. Although these erythrocytes have greater ability to accumulate amodiaquin than chloroquine, glucose has relatively less effect on amodiaquin accumulation than on chloroquine accumulation. In contrast to these findings with chloroquine-susceptible P. falciparum, glucose stimulates amodiaquin but not… 
Chloroquine susceptibility in malaria: dependence on exposure of parasites to the drug.
The hypothesis of inadequate exposure of intracellular parasites as the cause of chloroquine resistance to P. berghei is supported.
Primaquine synergises the activity of chloroquine against chloroquine-resistant P. falciparum.
Analysis of matched transfectants expressing mutant and wild-type alleles of the P. falciparum chlorquine resistance transporter indicate that primaquine exerts its activity by blocking PfCRT, and thus enhancing chloroquine accumulation, suggesting that a novel formulation of two antimalarial drugs already licensed for use in humans could be used to treat chloroquines-resistant parasites.
Chloroquine Resistance in Malaria: Accessibility of Drug Receptors to Mefloquine
Undiminished accumulation by erythrocytes infected with P. berghei CR provides an explanation for the superiority of mefloquine in treating chloroquine-resistant malaria.
Linkage of chloroquine resistance in Plasmodium berghei to infection of immature erythrocytes of mice.
Studies of infective potency were done to determine why chloroquine-resistant P. berghei is an obligate parasite of immature erythrocytes, indicating identical infective potencies which, in turn, indicates that chloroquin- resistant P. Berghei selects and preferentially infects immature eries whereas it rejects mature ery Throcytes.
Erythrocyte Surface: Novel Determinant of Drug Susceptibility in Rodent Malaria
Evidence is presented that erythrocyte surface components determine the affinity with which chloroquine is accumulated and thereby determine whether or not the malaria parasite will be susceptible to the drug.
Lysis of Plasmodium falciparum by ferriprotoporphyrin IX and a chloroquine-ferriprotoporphyrin IX complex
It is suggested that accumulation of this complex may account for the chemotherapeutic effect of chloroquine against P. falciparum by reducing the toxicity of FP and causing swelling and loss of internal detail in those that were identifiable.
A study of the uptake of chloroquine in malaria-infected erythrocytes. High and low affinity uptake and the influence of glucose and its analogues.
An absolute increase in the quantity of the low affinity site in erythrocytes parasitized with chloroquine-resistant P. berghei was noted, which may be related to an increase in quantity of parasite membrane.
Efflux pumps of antimalarial-resistance in Plasmodium falciparum
This review will concentrate the presentation mainly to experimentally supported evidence, as this represents the core of the present hypotheses on mechanisms of drug resistance in Plasmodium.
Malaria chemotherapy: resistance to quinoline containing drugs in Plasmodium falciparum.
Two major hypotheses have been proposed to account for the failure of CQ-resistant parasites to accumulate as much drug as their sensitive counterparts and the potential of pharmacological intervention to override these resistance mechanisms is discussed.
Cellular Uptake of Chloroquine Is Dependent on Binding to Ferriprotoporphyrin IX and Is Independent of NHE Activity in Plasmodium falciparum
There is definitive evidence that chloroquine (CQ) uptake in Plasmodium falciparum is determined by binding to ferriprotoporphyrin IX (FPIX), and diverse compounds that are known to disrupt lysosomal pH can mimic the verapamil effect are proposed.


-Chloroquine-14C was used to study the processes which concentrate chloroquine in mouse red blood cells infected with chloroquine-sensitive or with chloroquine-resistant Plasmodium berghei. The
High-affinity accumulation of chloroquine by mouse erythrocytes infected with Plasmodium berghei.
In studies of the CS model, certain compounds competitively inhibited chloroquine accumulation, while others did not, attributable to a specific receptor that imposes structural constraints on the process of accumulation.
Plasmodium falciparum in Owl Monkeys: Drug Resistance and Chloroquine Binding Capacity
Erythrocytes infected with chloroquine-sensitive Plasmodium falciparum bind chloroquine with an apparent intrinsic association constant of 1.5 x 107 liters per mole. Such high-affinity binding of
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