Mefloquine—An Aminoalcohol with Promising Antischistosomal Properties in Mice

Abstract

BackgroundThe 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 FindingsA 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/SignificanceOur 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.

Efficacy and side effects of praziquantel in the treatment of Schistosomiasis mansoni in schoolchildren in Shesha Kekele Elementary School, Wondo Genet, Southern Ethiopia

“…In areas with heavy transmission of schistosomiasis, it has been suggested that people might have been infected in the previous 3-5 weeks. Hence, such patients would harbor immature schistosomes that are less susceptible to PZQ [7,[39][40][41] . These immature stages have the high chance to survive a single treatment and mature to deposit eggs in the subsequent weeks.…”

“…Recently, schistosomicidal compounds such as artemether and mefloquine have been studied for their efficacy against schistosomes [6][7][8][9] . However, praziquantel (PZQ) remains the drug of choice in the treatment of schistosomiasis since the 1970s [10][11][12] .…”

Inhibitory Effects of Pepstatin A and Mefloquine on the Growth of Babesia Parasites

“…As described in a previous study, P. vinckei-infected mice treated with 50 mg/kg of pepstatin A showed no toxic signs, and the in vivo effect was improved by combinations of AP and peptidyl cysteine inhibitors. 20 Mefloquine was used for treatment of mice infected with Schistosoma mansoni and S. japonicum 43 and of hamsters infected with Opisthorchis viverrini 44 at concentrations of 100-400 mg/kg for 2-4 weeks. There were no signs of toxicity observed in the murine model.…”

The Use of Brazilian Medicinal Plants to Combat Schistosoma mansoni

“…activity (Rollas & Kuçukguzel, 2007). The most recent researches on new compounds or drugs with schistosomicidal activity have been carried out with: a) inhibitors of cysteine protease, such as K11777, considered a powerful schistosomicide that reduces the pathogenesis of experimental schistosomiasis (Abdulla et al, 2007), b) RNAi, in the attempt to develop drugs or compounds that act as enzyme silencers, e.g., the compound 4-phenyl-1,2,5-oxadiazole-3-carbonitrile-2-oxide, or furoxan, which acts on thioredoxin-glutathione reductase from S. mansoni (Kuntz et al, 2007, Sayed et al, 2008, c) trioxolanes or secondary ozonides (1, 2, 4-trioxolanes), which comprehend a class of synthetic endoperoxides that are cheap, easily synthesised, and similar to artemisinins, having activity on experimental infections with S. mansoni and S. japonicum (Caffrey, 2007, Xiao et al, 2007, d) mefloquine (antimalarial), which showed schistosomicidal activity against young and adult S. mansoni worms (Van Nassauw et al, 2008, Keiser et al, 2009), e) arachidonic acid, which showed schistosomicidal properties against S. mansoni and S. haematobium ( E l R i d i e t a l . , 2010), and f) miltefosine (antileishmania), which reduced the parasite burden of mice infected with S. mansoni (Eissa et al, 2011).…”