INDEX Chloroquine

Fig. 2 Distribution of the sorted version of the P values for all reactions of the parasite for the tetracycline treatment (a) and the chloroquine treatment (b) compared with control. Each gene indexed is plotted on the /-axis and its corresponding Wilcoxon Pvalue is plotted on the y-axis...

The most specific metabolizing enzyme is imidazole N-methyl-transferase ( histamine acetylase ), which can be inhibited in vivo by amodiaquine, chloroquine and metoprine. Histamine is also metabolized by hlstaminase , and this enzyme can be inhibited by aminoguanidine, metronidazole and pentamidine (see diamine oxidase inhibitors). Metabolites in the urine can be measured to give some index of histamine turnover. 

The IC50 values are expressed as meaniS.D. of three different determinations per experiment SI, the Selectivity Index, is defined as the ratio of the CC50 value determined on the mammalian cell line to that of the IC50 value determined on the CQ-sensitive P. falciparum (D6). Two reference drugs, chloroquine and artemisinin, are included as positive controls and their IC50 values are given in ng/ml. nd not determined. 

This could not be the case of homofascaplysin A (39) [Fig. (11)], a p-carboline-indole alkaloid isolated from the sponge Hyrtios erecta [56], Indeed, homofascaplysin A (39) showed activity against chloroquine-resistant P. falciparum strains with an IC50 of about 20 ng/mL, but its toxicity toward rat skeletal muscle myoblast cells was estimated to be less than 1 pg/mL, and thus the selectivity index of this molecule is very narrow. 

The half-life of mefloquine in the human body averages 15 days. Unlike quinine, it has a very high therapeutic index. Intensive clinical studies have shown it to be safe and effective in curing both falciparum and vivax types of malaria, regardless of whether these are resistant to chloroquine. Fears that resistance to mefloquine would be initiated by indiscriminate use of this drug are limiting its curative use to areas where chloroquine-resistant strains of Plasmodium flourish. Yor prophylactic use in such areas, it is combined with the pyrimethamine-sulfadoxine pair to decrease likelihood of resistance developing, in accord with principles discussed in Section 6.5. For clinical details, see Schmidt et al. (1978) for the overall picture on mefloquine, see WHO (1983). 

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