Effect of closantel on intrategumental pH in Schistosoma mansoni and Fasciola hepatica

It has been proposed that the anthelmintic activity of the flukicide, closantel, is due to the drug's ability to interfere with the proton gradient in the parasite's mitochondria that in turn inhibits the generation of ATP by the parasite. Recent results using 31P-NMR suggest that this is not the primary target of the drug. We measured the effects of closantel on fluke intrategumental pH and observed a significant decrease (6.8 to 6.5). This decrease occurred within 10 min and at concentrations that were lower than those that produced significant changes in parasite ATP concentration. We also noted that this drug-induced change in intrategumental pH was associated with a marked reduction in fluke motility. Our results, when coupled to previous reports, would suggest that closantel is a membrane-active molecule that is capable of affecting a number of helminth biochemical and physiological processes.