Chloroquine interaction

Guiserix J, Aizel A. Interactions ciclosporine-chloroquine. [Cyclosporine-chloroquine interactions.] Presse Med 1996 25(26) 1214. 

Menting, J.G., Tilley, L., Deady, L.W., et al. (1997) The antimalarial drug, chloroquine, interacts with lactate dehydrogenase from Plasmodium falciparum. Mol. Biochem. Parasitol. 88, 215-224. 

Chloroquine is contraindicated in patients with known hypersensitivity. Precautions and interactions for chloroquine are provided in the discussion of the drug in the Antimalatial Dragp section. 

El-Ashry et al. [36] studied the complex formation between the bromophenol blue, primaquine, and other important aminoquinoline antimalarials. The colorimetric method used was described as simple and rapid and is based on the interaction of the drug base with bromophenol blue to give a stable ion-pair complex. The spectra of the complex show maxima at 415 420 nm with high apparent molar absorptivities. Beer s law was obeyed in the concentration range 1-8,2-10, and 2-12 pg/mL for amodiaquine hydrochloride, primaquine phosphate, and chloroquine phosphate, respectively. The method was applied to the determination of these drugs in certain formulations and the results were favorably comparable to the official methods. 

P.-G. Wu, L. Song, J. B. Clendenning, B. S. Fujimoto, A. S. Benight, and J. M. Schurr, Interaction of chloroquine with linear and supercoiled DNAs. Effect on the torsional dynamics, rigidity, and twist energy parameter, Biochemistry 27, 8128-8144 (1988). 

Quinine is the principal alkaloid derived from the bark of the cinchona tree. It has been used for malaria suppression for over 300 years. By 1959 it was superseded by other drugs, especially chloroquine. After widespread resistance to chloroquine became manifest quinine again became an important antimalarial. Its main uses are for the oral treatment of chloroquine-resistant falciparum malaria and for parenteral treatment of severe attacks of falciparum malaria. Quinine is a blood schizonticide with some gametocytocidal activity. It has no exoerythrocytic activity. Its mechanism of action is not well understood. It can interact with DNA, inhibiting strand separation and ultimately protein synthesis. Resistance of quinine has been increasing in South-East Asia. 

Chloroquine (Aralen) is one of several 4-aminoquino-line derivatives that display antimalarial activity. Chloroquine is particularly effective against intraerythrocytic forms because it is concentrated within the parasitized erythrocyte. This preferential drug accumulation appears to occur as a result of specific uptake mechanisms in the parasite. Chloroquine appears to work by intercalation with DNA, inhibition of heme polymerase or by interaction with Ca++-calmodulin-mediated mechanisms. It also accumulates in the parasite s food vacuoles, where it inhibits peptide formation and phospholipases, leading to parasite death. 

For over 300 years, the quinoline family of drugs, and chloroquine in particular, has been used as the primary treatment for malaria. Recent studies have demonstrated that this drug inhibits the aggregation of free heme into hemozoin, allowing levels of monomeric heme to rise until cell lysis occurs. Although the determined structure of hemozoin makes the polymer termination scheme proposed by Sullivan et al. unlikely, hemozoin drug heme interactions appear critical in the inhibition mechanism. Thus, researchers have identified the characteristics of... 

Chloroquine drastically improves the transfection of cells when DNA/polylysine conjugates are used (Zenke et al., 1990 Midoux et al., 1993). So far, the mechanism of action of chloroquine has not been completely elucidated. Chloroquine is supposed to protect the internalized plasmid from intracellular degradation as a result of the neutralization of acidic compartments and the inhibition of endosome fusion with lysosomes. Furthermore, the swelling of vesicles can be induced when the concentration of chloroquine is high enough. However, there is no direct relationship between the neutralization of the acidic cell compartments and the transfection efficiency (Erbacher et al., 1996a). Once taken up by the cells, chloroquine accumulates inside acidic vesicles where it can reach a concentration more than 50 mM, based on the estimated volume of the vesicular compartments. At physiological pH, 82% of chloroquine is protonated and can bind to nucleic acids. Therefore, the interaction of chloroquine with DNA appears to be... 

In the first model, we sought to reveal subgraphs of a biological interaction network that show substantial adaptations when cells transcriptionally respond to a changing environment or treatment. As a case study, we investigated the response of the malaria parasite Plasmodium falciparum to chloroquine and tetracycline treatments. 

Praziquantel Interactions of this drug are reported with carbamazepine, phenytoin, dexamethasone, and chloroquine.182... 

The mechanism by which PfCRT confers resistance to chloroquine is still under discussion [75], The first aspect concerns the nature of the protein whether PfCRT, postulated to possess ten transmembrane helices, is considered as a member of the drug-metabolite transporter family of proteins [55, 76-78], Some authors discuss about the channel nature of the protein [79, 80], It has been suggested that the change of the charged lysine to uncharged threonine affects the electrostatic interaction with the diprotonated CQ [81]. In the mutated forms, the absence of electrostatic interactions allows the drug to cross the channel (Fig. 6). This results in the efflux of the drug out of the DV [81]. Note here that the reduced accumulation can be partially reversed by verapamil, a lipophilic compound (Fig. 5). 

GRAPEFRUIT JUICE CHLOROQUINE t plasma concentrations of chloroquine (AUC 11.3-fold, t maximum concentration). The interaction has not been studied in patients with malaria Due to inhibition of metabolism of chloroquine Be aware... 

---