The (+)-isomers of mefloquine and its threo analog are 1.69 to 1.95 times more active than the (-)-isomers against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum in vitro. This large a differential between the activity of (+)- and (-)-isomers was not observed for other synthetic amino alcohol antimalarial agents containing a piperidine ring. The enantiomers of amino alcoh...

We have used a specific inhibitor of the malarial aspartic proteinase plasmepsin I and a nonspecific cysteine proteinase inhibitor to investigate the importance of hemoglobin degradation in the mechanism of action of chloroquine, amodiaquine, quinine, mefloquine (MQ), halofantrine, and primaquine. Both proteinase inhibitors antagonized the antiparasitic activity of all drugs tested with the exc...

Two chloroquine-resistant cloned isolates of Plasmodium falciparum were subjected to mefloquine selection to test if this resulted in alterations in chloroquine sensitivity and amplification of the pfmdr1 gene. The mefloquine-resistant lines derived by this selection were shown to have amplified and overexpressed the pfmdr1 gene and its protein product (Pgh1). Macrorestriction maps of chromosom...

The current study has examined whether drugs that are transported to the systemic circulation via intestinal lymph (and therefore associate with lipoproteins within enterocyte) accessible enterocyte-based metabolic processes. impact of changes mass lipid present precursor pool (LLPP) on extent drug metabolism also been addressed. Low (5 mg oleic acid/h) or high [20 acid/5.2 lyso-phosphatidylcho...