Mefloquine--an aminoalcohol with promising antischistosomal properties in mice

• Published in: PLoS neglected tropical diseases Vol. 3; no. 1; p. e350
• Main Authors: Keiser, Jennifer, Chollet, Jacques, Xiao, Shu-Hua, Mei, Jin-Yan, Jiao, Pei-Ying, Utzinger, Jürg, Tanner, Marcel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2009; Public Library of Science (PLoS)
• Subjects: Administration, Oral; Animals; Antiparasitic agents; Disease control; Disease prevention; Dose-Response Relationship, Drug; Drug dosages; Drug Evaluation, Preclinical; Drug resistance; Female; Infectious Diseases/Antimicrobials and Drug Resistance; Malaria; Male; Mefloquine - administration & dosage; Mefloquine - chemistry; Mefloquine - pharmacology; Mice; Mice, Inbred Strains; Parasites; Parasitic diseases; Pharmaceutical industry; Schistosoma japonicum - drug effects; Schistosoma mansoni; Schistosoma mansoni - drug effects; Schistosomicides - administration & dosage; Schistosomicides - chemistry; Schistosomicides - pharmacology; Tropical diseases; Dose-Response Relationship, Drug; Schistosoma mansoni; Animals; Mefloquine; Administration, Oral; Female; Male; Mice; Drug Evaluation, Preclinical; Mice, Inbred Strains; Schistosoma japonicum; Schistosomicides
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0000350

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. 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. 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.