Author(s): Ye ZG, Van Dyke K
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Abstract 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.
This article was published in Biochem Biophys Res Commun
and referenced in Malaria Control & Elimination