title: Light and scanning electron microscopy studies on the effects of the enantiomers of praziquantel and its main metabolite on Schistosoma mansoni in vitro.
abstract: In the present study, the effects of the enantiomers of the anthelmintic drug praziquantel (PZQ) and its main metabolite trans-4-hydroxy-praziquantel (TRANS) on pairs of Schistosoma mansoni worms were examined in vitro. Highly purified enantiomers (optical purity, greater than 99.9% for PZQ and 99.0% for TRANS) were used. Paired worms were incubated for 4 h in RPMI medium containing 0.01, 0.02, 0.075, 0.1, 2.5, 10, and 100 micrograms PZQ or TRANS enantiomers/ml, respectively, before being transferred to drug-free medium for another 20 h. PZQ is used as a racemate in the therapy, and its effect is attributed to the R(-)-enantiomer. R(-)-PZQ and R(-)-TRANS proved to be at least 10(5) times more effective than the respective S(+)enantiomers, causing tegumental damage and surface blebbing on S. mansoni. As judged from the effective doses in 50% of the worms (ED50 values); R(-)-PZQ and R(-)-TRANS showed nearly the same efficacy against adult S. mansoni. Male worms reacted more sensitively than did females. As determined by scanning electron microscopy, alterations in lethally damaged worms depended on the drug used, even following incubation at the lowest concentration tested (0.01 microgram/ml). Worms exposed to R(-)-TRANS were elongated, whereas treatment with R(-)-PZQ led to contractions and twisted parasites. Both compounds caused excessive surface blebbing along the dorsal side of the worms' tegument.
authors.affiliation: Institut für Pharmazeutische Chemie der Westfälischen Wilhelms-Universität, Münster, Federal Republic of Germany.
authors.forename: U
authors.initials: U
authors.lastname: Staudt
authors.forename: G
authors.initials: G
authors.lastname: Schmahl
authors.forename: G
authors.initials: G
authors.lastname: Blaschke
authors.forename: H
authors.initials: H
authors.lastname: Mehlhorn
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D008855:Microscopy, Electron, Scanning; D011223:Praziquantel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: C067550:4-hydroxypraziquantel; D011223:Praziquantel