Abstract
Citalopram, is an extremely potent inhibitor of neuronal serotonin reuptake. It is structurally unrelated to other antidepressants, but it contains the chemical features associated with reversal of drug resistance and exhibits minimal cardiotoxic side effects and fewer of the anticholinergic and adrenolytic side effects associated with other psychotropic agents. Sensitivity tests to citalopram alone and in combination with chloroquine were performed against chloroquine-resistant and chloroquine-sensitive strains ofPlasmodium falciparum and Plasmodium chabaudi. Citalopram alone showed intrinsic activity against the chloroquine-resistant strains of P. falciparum(IC50 = 1.51 ± .6 μM) but only limited activity against the chloroquine-sensitive strain (IC50 = 33.27 ± 5.87 μM) and no activity in vivo. The interaction of chloroquine and citalopram in vitro resulted in a synergistic response in the chloroquine-resistant strain but there was no interaction between the drugs in the chloroquine-sensitive strain—a pattern found with other reversal agents. Citalopram enhanced chloroquine susceptibility in both strains of P. chabaudi, however, the potentiating effect was seen at lower doses in the chloroquine-resistant strain. The results of this study suggest that citalopram may have potential as a chemosensitizer inPlasmodium infections on the basis of the low toxicity of citalopram at concentrations potentiating chloroquine activity bothin vitro and in vivo.
Footnotes
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Send reprint requests to: Dr. S. Evans, Department of Experimental and Clinical Pharmacology, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa.
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↵1 This work was supported by Lundbeck.
- Received December 2, 1996.
- Accepted March 12, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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