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Synergism of Cimetidine with Anti-Malarial Agents
Alex Paciorkowski, Wei-Wei Dai, Anthony Cerami and Bradley J. Berger
The Journal of Parasitology
Vol. 83, No. 5 (Oct., 1997), pp. 960-963
Stable URL: http://www.jstor.org/stable/3284300
Page Count: 4
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The histamine type-2 receptor antagonist and cytochrome P450 inhibitor cimetidine was examined for its antimalarial properties in the presence or absence of chloroquine or pyrimethamine. When used alone, cimetidine displayed little activity against a number of Plasmodium falciparum clones in vitro, with an IC50 of 300-700 µM. The compound was found to be highly synergistic in combination with chloroquine and also displayed a degree of synergism when used in combination with pyrimethamine. These synergistic effects were independent dent of the chloroquine- or pyrimethamine-resistance status of the clones. The cytochrome P450 inhibitor proadifen displayed weak synergism or antagonism with chloroquine, depending on the clone tested, and clear antagonism with pyrimethamine. The results with proadifen indicate that cimetidine was exerting its synergistic activity via a mechanism distinct from inhibition of cytochrome P450. Additional experiments have demonstrated that cimetidine interferes with neither plasmodial sterol metabolism nor heme polymerization.
The Journal of Parasitology © 1997 The American Society of Parasitologists