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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Reversal of chloroquine resistance in falciparum malaria independent of calcium channels.

Racemic verapamil and close structural derivatives gallopamil and devapamil completely reverse chloroquine-resistance in falciparum malaria at 1-2 micromolar concentrations. If the R-(+) isomers of these calcium channel inhibitors are used, chloroquine-resistance is again completely reversed at similar doses. However, these R-(+) isomers do not bind to cardiovascular calcium channels which are stereospecific for the S-(-) isomer of the drugs. Further since calcium channel inhibition is not involved, toxicity associated with this activity can be avoided. Therefore it is possible that a series of R-(+) isomers could be found that alter the resistant state without possessing significant toxicity. It is postulated that these lipophilic drugs are interacting with the mechanism of resistance, possibly a multidrug resistance glycoprotein pump.[1]

References

  1. Reversal of chloroquine resistance in falciparum malaria independent of calcium channels. Ye, Z.G., Van Dyke, K. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
 
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