Antimalarial agents. Chloroquine, hydroxychloroquine, and quinacrine

Tanenbaum, Laura M.

doi:10.1001/archderm.116.5.587

Cited by 83 publications

(54 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…7) and low IC 50 s (Table 2) in field isolates. QC was the antimalarial drug of choice prior to CQ and is structurally similar to CQ, save for an additional benzene ring (33). Both CQ and QC are known to bind to heme and inhibit its degradation and detoxification (34).…”

Section: Discussionmentioning

confidence: 99%

A High-Content Phenotypic Screen Reveals the Disruptive Potency of Quinacrine and 3′,4′-Dichlorobenzamil on the Digestive Vacuole of Plasmodium falciparum

Lee

Goh

Ch'ng

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Plasmodium falciparum is the etiological agent of malignant malaria and has been shown to exhibit features resembling programmed cell death. This is triggered upon treatment with low micromolar doses of chloroquine or other lysosomotrophic compounds and is associated with leakage of the digestive vacuole contents. In order to exploit this cell death pathway, we developed a high-content screening method to select compounds that can disrupt the parasite vacuole, as measured by the leakage of intravacuolar Ca 2؉ . This assay uses the ImageStream 100, an imaging-capable flow cytometer, to assess the distribution of the fluorescent calcium probe Fluo-4. We obtained two hits from a small library of 25 test compounds, quinacrine and 3=,4=-dichlorobenzamil. The ability of these compounds to permeabilize the digestive vacuole in laboratory strains and clinical isolates was validated by confocal microscopy. The hits could induce programmed cell death features in both chloroquine-sensitive and -resistant laboratory strains. Quinacrine was effective at inhibiting field isolates in a 48-h reinvasion assay regardless of artemisinin clearance status. We therefore present as proof of concept a phenotypic screening method with the potential to provide mechanistic insights to the activity of antimalarial drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

A High-Content Phenotypic Screen Reveals the Disruptive Potency of Quinacrine and 3′,4′-Dichlorobenzamil on the Digestive Vacuole of Plasmodium falciparum

Lee

Goh

Ch'ng

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…As far as is known, chloroquine forms complexes with gangliosides, inhibiting further degradation [38] and finally leading to an accumulation of lipid complexes in the neuroretina [39,40]. Ultimately this may cause irreversible damage to rods and cones even after cessation of the drug [41,42].…”

Section: Toxicitymentioning

confidence: 99%

The Multifocal Pattern Electroretinogram in Chloroquine Retinopathy

Neubauer

Stiefelmeyer²,

Berninger³

et al. 2004

Ophthalmic Res

View full text Add to dashboard Cite

Purpose: Optimal screening for ocular toxicity caused by chloroquine and hydroxychloroquine is still controversial. With the multifocal pattern electroretinogram (mfPERG), a new electrophysiological technique has recently become available to detect early changes of ganglion cells. In this study this new technique is applied to a series of 10 patients seen consecutively receiving long-term chloroquine medication. Methods: In 10 patients receiving chloroquine medication, clinical examination, Amsler visual field testing and computerized color vision testing were performed. If toxicity was suspected, automated perimetry was carried out. In addition, in all patients conventional pattern electroretinogram (PERG) and mfPERG testing were performed. Results: On clinical examination 8 patients showed no chloroquine-associated maculopathy, while 2 patients did. Of these 2, only 1 reported abnormalities when viewing the Amsler chart, while automated perimetry showed typical, ring-like paracentral scotomas in both affected patients and color vision was significantly abnormal. In the normal patients, 4 of 8 had a mild color vision disturbance, which correlated to age-related macular changes. The amplitudes of the PERG and the central (approximately 10°) responses of the mfPERG were markedly reduced in chloroquine maculopathy, while the latencies were unchanged. The peripheral rings of mfPERG (ranging to 48°) were not affected by chloroquine toxicity. Both PERG and mfPERG were less affected by age-related macular changes. Conclusions: The reduction of PERG and central mfPERG responses in chloroquine maculopathy may help with the early detection of toxicity.

show abstract

“…Adverse effects are relatively uncommon when chloroquine is used for antimalarial chemoprophylaxis and they usually develop after long-term administration. Although epidemiological studies did not confirm chloroquine as a cause of agranulocytosis and/or bone marrow aplasia (1,2), chloroquine is nevertheless listed among myelotoxic drugs (3)(4)(5)(6). Moderate neutropenia has been reported in 4.8% of rheumatoid patients treated with 250 mg chloroquine daily for over 1 year (7).…”

Section: Discussionmentioning

confidence: 99%

Bone marrow aplasia following acute poisoning with chloroquine-proguanil

Payen¹,

Monnin²,

Pulce³

et al. 2008

Clinical Toxicology

View full text Add to dashboard Cite

Acute poisonings involving chloroquine are common in sharp contrast to those involving proguanil, another antimalarial drug. A 39-yearold woman ingested a combination of 11.2 g chloroquine and 22.4 g proguanil (i.e., 112 tablets of the commercial product Savarine ® ). She presented with cardiovascular disorders typically associated with chloroquine overdose, but unexpectedly bone marrow aplasia developed on day 3 post-ingestion that required granulocyte-colony stimulating factor administration, and recovered on days 10-14. Toxicological analysis evidenced both chloroquine and proguanil in the patient's serum and ruled out the involvement of any major myelotoxic drug. This is seemingly the first report of bone marrow aplasia following acute poisoning with chloroquine and proguanil. The antifolinic effect of proguanil is hypothesized to have potentiated the still debated myelotoxicity of chloroquine in this patient.

show abstract

Antimalarial agents. Chloroquine, hydroxychloroquine, and quinacrine

Cited by 83 publications

References 52 publications

A High-Content Phenotypic Screen Reveals the Disruptive Potency of Quinacrine and 3′,4′-Dichlorobenzamil on the Digestive Vacuole of Plasmodium falciparum

A High-Content Phenotypic Screen Reveals the Disruptive Potency of Quinacrine and 3′,4′-Dichlorobenzamil on the Digestive Vacuole of Plasmodium falciparum

The Multifocal Pattern Electroretinogram in Chloroquine Retinopathy

Bone marrow aplasia following acute poisoning with chloroquine-proguanil

Contact Info

Product

Resources

About