Springer Online Journal Archives 1860-2000
Abstract In the present study, the effects of the enantiomers of the anthelmintic drug praziquantel (PZQ) and its main metabolitetrans-4-hydroxypraziquantel (TRANS) on pairs ofSchistosoma mansoni worms were examined in vitro. Highly purified enantiomers (optical purity, 〉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 μg PZQ or TRANS enantiomers/ml, respectively, before being transferred to drug-free medium for another 20 h. PZQ is used as a racementa in the therapy, and its effect is attributed to the R(−)-enantiomer. R(−)-PZQ and R(−)-TRANS proved to be at least 105 times more effective than the respective S(+)enantiomers, causing tegumental damage and surface blebbing onS. 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 adultS. 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 μg/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.
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