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Mefloquine--an aminoalcohol with promising antischistosomal properties in mice.

Keiser J, Chollet J, Xiao SH, Mei JY, Jiao PY, Utzinger J, Tanner M - PLoS Negl Trop Dis (2009)

Bottom Line: Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent S. mansoni infection.Our findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality.Further in vitro and in vivo studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on S. haematobium and other trematodes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Basel, Switzerland. jennifer.keiser@unibas.ch

ABSTRACT

Background: The treatment and control of schistosomiasis, an often neglected tropical disease that exacerbates poverty, depends on a single drug, praziquantel. The large-scale use of praziquantel might select for drug-resistant parasites, hence there is a need to develop new antischistosomal compounds. Here, we report that the antimalarial drug mefloquine possesses promising antischistosomal properties in mice.

Methodology/principal findings: A single dose of mefloquine (200 or 400 mg/kg) administered orally to mice infected with adult Schistosoma mansoni or adult S. japonicum resulted in high or complete total and female worm burden reductions (72.3%-100%). Importantly, high worm burden reductions were also observed for young developing stages of S. mansoni and S. japonicum harbored in the mouse. Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent S. mansoni infection.

Conclusions/significance: Our findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality. Further in vitro and in vivo studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on S. haematobium and other trematodes. It will be interesting to investigate whether mefloquine, which is widely and effectively used for the treatment of malaria, has an impact on schistosomiasis in areas where both malaria and schistosomiasis co-exist.

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Related in: MedlinePlus

Chemical structures of mefloquine, quinine, halofantrine, and lumefantrine.
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pntd-0000350-g001: Chemical structures of mefloquine, quinine, halofantrine, and lumefantrine.

Mentions: The in vivo antischistosomal efficacy of 11 antimalarial drugs is summarized in Tables 1 and 2. Drugs were administered orally at a single dose of 400 mg/kg to mice harboring adult S. mansoni, and worm burden reductions, including changes in worm distributions, were assessed. Amodiaquine, atovaquone, lumefantrine, pyrimethamine, pyronaridine, sulfadoxine, and sulfamethoxypyrazine showed no antischistosomal activity. Quinine and halofantrine resulted in total and female worm burden reductions ranging between 51.7% and 74.9% and changes in the worm distribution. The highest activity (total and female worm burden reduction of 77.3% and 100%, respectively) was observed with a single dose of mefloquine (400 mg/kg), which was statistically significant (p<0.05). The chemical structures of the four aminoalcohols quinine, halofantrine, lumefantrine, and mefloquine are shown in Figure 1.


Mefloquine--an aminoalcohol with promising antischistosomal properties in mice.

Keiser J, Chollet J, Xiao SH, Mei JY, Jiao PY, Utzinger J, Tanner M - PLoS Negl Trop Dis (2009)

Chemical structures of mefloquine, quinine, halofantrine, and lumefantrine.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600813&req=5

pntd-0000350-g001: Chemical structures of mefloquine, quinine, halofantrine, and lumefantrine.
Mentions: The in vivo antischistosomal efficacy of 11 antimalarial drugs is summarized in Tables 1 and 2. Drugs were administered orally at a single dose of 400 mg/kg to mice harboring adult S. mansoni, and worm burden reductions, including changes in worm distributions, were assessed. Amodiaquine, atovaquone, lumefantrine, pyrimethamine, pyronaridine, sulfadoxine, and sulfamethoxypyrazine showed no antischistosomal activity. Quinine and halofantrine resulted in total and female worm burden reductions ranging between 51.7% and 74.9% and changes in the worm distribution. The highest activity (total and female worm burden reduction of 77.3% and 100%, respectively) was observed with a single dose of mefloquine (400 mg/kg), which was statistically significant (p<0.05). The chemical structures of the four aminoalcohols quinine, halofantrine, lumefantrine, and mefloquine are shown in Figure 1.

Bottom Line: Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent S. mansoni infection.Our findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality.Further in vitro and in vivo studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on S. haematobium and other trematodes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Basel, Switzerland. jennifer.keiser@unibas.ch

ABSTRACT

Background: The treatment and control of schistosomiasis, an often neglected tropical disease that exacerbates poverty, depends on a single drug, praziquantel. The large-scale use of praziquantel might select for drug-resistant parasites, hence there is a need to develop new antischistosomal compounds. Here, we report that the antimalarial drug mefloquine possesses promising antischistosomal properties in mice.

Methodology/principal findings: A single dose of mefloquine (200 or 400 mg/kg) administered orally to mice infected with adult Schistosoma mansoni or adult S. japonicum resulted in high or complete total and female worm burden reductions (72.3%-100%). Importantly, high worm burden reductions were also observed for young developing stages of S. mansoni and S. japonicum harbored in the mouse. Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent S. mansoni infection.

Conclusions/significance: Our findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality. Further in vitro and in vivo studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on S. haematobium and other trematodes. It will be interesting to investigate whether mefloquine, which is widely and effectively used for the treatment of malaria, has an impact on schistosomiasis in areas where both malaria and schistosomiasis co-exist.

Show MeSH
Related in: MedlinePlus