Experimental chemotherapy of schistosomiasis mansoni. XIII. Activity of praziquantel, an isoquinoline-pyrazino derivative, on mice, hamsters and Cebus monkeys.
In mice experimentally infected with Schistosoma mansoni, praziquantel (2-cyclohexylcarbonyl-1,3,4,6,7,11b-hexahydro-2H-pyrazino[2,1-a]isoquinoline-4-one), administered orally at the levels of 100 and 50 mg/kg, for 5 consecutive days, produces oogram changes in all animals and a pronounced hepatic shift of schistosomes (97.1 and 89.1, respectively). At lowest levels (12.5 and 6.3 mg/kg), alterations in the oogram could still be detected, although hepatic shift of schistosomes was no more evident. After a single intramuscular injection, the results obtained paralleled those observed with a single-dose oral treatment. The hepatic shift was only moderate at 200 and 100 mg/kg and the percentages of worms retained in the liver, after perfusion, were particularly low. When nasal route in a 1-day regimen was used, the results obtained were slightly less evident as compared with those observed by oral route (5-day schedule). Considering the percentage of oogram changes, the degree of hepatic shift of schistosomes and the percentage of worms fixed in the liver, the antischistosomal activity of praziquantel was greater in hamsters than in mice. Actually, a daily dose as low as 12.5 mg/kg, administered for 5 consecutive days, was sufficient to shift 60.4% of the worms towards the liver and to produce alterations of the oogram in 60% of the animals. In Cebus monkeys orally treated with 10 and 20 mg/kg of praziquantel, given 3 times within a single day (total doses of 30 and 60 mg/kg, respectively), a remarkable reduction in worm burden was observed. A single oral or intramuscular dose of 100 mg/kg was found to be curative. One Cebus doses with 100 mg/kg, by nasal spray, was found to harbor only female worms at autopsy performed 69 days after treatment.
D000818:Animals; D006224:Cricetinae; D000882:Haplorhini; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D012550:Schistosoma mansoni / Q000187:drug effects; D012552:Schistosomiasis / Q000188:drug therapy*; D012556:Schistosomicides / Q000627:therapeutic use*
D007546:Isoquinolines; D011719:Pyrazines; D012556:Schistosomicides