Summary
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, produced 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 dosed with 100 mg/kg, by nasal spray, was found to harbor only female worms at autopsy performed 69 days after treatment.
Zusammenfassung
Verabreichung von Praziquantel (2-Cyclohexylcarbonyl-1,3,4,6,7,11b-hexahydro-2H-pyrazino[2,1-a]isochinolin-4-on) an experimentell mit Schistosoma mansoni infizierte Mäuse in oralen Dosen von 100 bzw. 50 mg/kg an jeweils fünf aufein and erfolgenden Tagen verursachte bei allen Tieren Oogrammveränderungen und eine deutliche Verschiebung der Schistosomen (97,1 bzw. 89,1%) in die Leber. Auch bei den niedrigsten Dosen (12,5 und 6,3 mg/kg) wurden noch Oogrammveränderungen beobachtet, aber keine “liver shift” mehr. Nach einmaliger intramuskulärer Injektion ergaben sich vergleichbare Ergebnisse wie bei einmaliger oraler Gabe. Die “liver shift” nach Gabe von 200 bzw. 100 mg/kg war nur mäßig und der Anteil der nach Perfusion in der Leber zurückbleibenden Schistosomen besonders niedrig. Bei einmaliger nasaler Behandlung waren die Ergebnisse nicht ganz so gut wie nach oraler Gabe an fünf Tagen.
Gemessen am Anteil der Tiere mit Oogrammveränderungen, dem Ausmaß der “liver shift” der Schistosomen und dem Prozentsatz der in der Leber fixierten Würmer ist Praziquantel im Hamster wirksamer gegen Schistosomen als in der Maus. Schon eine an fünf Tagen gegebene Dosis von 12,5 mg/kg bewirkte eine “liver shift” von 60,4% der Würmer und Oogrammveränderungen bei 60% der Tiere.
Im Cebus-Affen wurde nach dreimaliger Gabe von 10 bzw. 20 mg/kg an einem Tag (Gesamtdosis 30 bzw. 60 mg/kg) eine bemerkenswerte Reduktion der Wurmzahl gefunden. Eine einmalige orale oder intramuskuläre Gabe von 100 mg/kg bewirkte eine Heilung. Ein Affe zeigte nach Behandlung mit 100 mg/kg in Form eines Nasensprays bei der Sektion nach 69 Tagen nur weibliche Schistosomen.
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References
Baxter, S.A.R., Richards, H.C.: Schistosomicides. I. Derivatives of 2-aminomethyl-1,2,3,4-tetrahydroquinoline. J. med. Chem. 14, 1033–1042 (1971)
Christopherson, J.B.: The successful use of antimony in bilharziasis. Lancet 1918, 325–327
Cunha, A.S.: Esquistossomose mansoni, p. 435. São Paulo, Brazil: Universidade de São Paulo 1970
Foster, R.: The preclinical development of oxamniquine. Rev. Inst. Med. trop. S. Paulo 15 (Suppl. 1), 1–9 (1973)
Foster, R., Cheetham, B.L., King, D.F., Mesmer, E.T.: The action of UK 3883, a novel 2-aminotetrahydroquinoline derivative, against mature schistosomes in rodents and primates. Ann. trop. Med. Parasit. 65, 59–70 (1971a)
Foster, R., Mesmer, E.T., Cheetham, B.L., King, D.F.: The control of immature Schistosoma mansoni in mice by UK 3883, a novel 2-aminotetrahydroquinoline derivative. Ann. trop. Med. Parasit. 65, 221–232 (1971b)
Gönnert, R., Andrews, P.: Praziquantel, a new broad-spectrum antischistosomal agent. Z. Parasitenk. 52, 129–150 (1977)
Jaffe, J.J., Doremus, H.M., Dunsford, H.A., Meymerian, E.: Long-term efficacy of tubercidin against schistosomiasis japonica and mansonica in primates. Amer. J. trop. Med. Hyg. 24, 289–297 (1975)
Jaffe, J.J., Meymerian, E., Doremus, H.M.: Antischistosomal action of tubercidin administered after absorption into red cells. Nature 230, 408–409 (1971)
James, C., Webbe, G., Nelson, G.S.: The susceptibility to praziquantel of Schistosoma haematobium in the baboon (Papio anubis) and of S. japonicum in the vervet monkey (Cercopithecus aethiops). Z. Parasitenk. 52, 179–195 (1977)
Katz, N., Pellegrino, J.: Estudo de alguns aspectos da esquistossomose mansoni em macacos Cebus pelo método do oograma quantitativo. Rev. Inst. Med. trop. S. Paulo 16, 245–252 (1974)
Katz, N., Pellegrino, J., Grinbaum, E., Chaves, A., Zicker, F.: Further clinical trials with oxamniquine, a new antischistosomal agent. Rev. Inst. Med. trop. S. Paulo 15 (Suppl. 1), 35–41 (1973)
Katz, N., Pellegrino, J., Memória, J.M.P.: Quantitative oogram method in Cebus monkeys experimentally infected with Schistosoma mansoni. J. Parasit. 52, 917–919 (1966)
Kaye, B., Woolhouse, N.M.: The metabolism of a new schistosomicide. 2-isopropylaminomethyl-6-methyl-7-nitro-1,2,3,4-tetrahydroquinoline (U.K. 3883). Xenobiotica 2, 169–178 (1972)
Kikuth, W., Gonnert, R.: Experimental studies on the therapy of schistosomiasis. Ann. trop. Med. Parasit. 42, 256–267 (1948)
Kikuth, W., Gonnert, R., Mauss, H.: Miracil, ein neues Chemotherapeuticum gegen die Darmbilharziose. Naturwissenschaften 33, 253–254 (1946)
Lambert, C.R., Stauffer, P.: Chemotherapy of experimental Schistosoma mansoni infections with a nitrothiazole derivative, CIBA 32,644-Ba. Ann. trop. Med. Parasit. 58, 292–303 (1964)
Lambert, C.R., Wilhelm, M., Striebel, H., Kradolfer, F., Schmidt, P.: Eine neue gegen Bilharziose und Amoebiase wirksame Verbindung. Experientia (Basel) 20, 452–453 (1964)
Mauss, H.: Über basisch substituierte Xanthon- und Thioxanthon-Abkömmlinge; Miracil, ein neues J. Chemotherapeuticum. Chem. Ber. 81, 19–31 (1948)
Pellegrino, J., De Maria, M., Faria, J.: Infection of the golden hamster with Schistosoma mansoni cercaria through the cheek pouch. J. Parasit. 51, 1015 (1965)
Pellegrino, J., Faria, J.: The oogram method for the screening of drugs in schistosomiasis mansoni. Amer. J. trop. Med. Hyg. 14, 363–369 (1965)
Pellegrino, J., Katz, N.: Experimental chemotherapy of schistosomiasis mansoni. In: Ben Dawes, ed. Advanc. Parasit. 6, p. 233–291. London, New York: Academic Press 1968
Pellegrino, J., Katz, N.: Experimental chemotherapy of schistosomiasis. V. Laboratory trials with UK 3883, a 2-aminotetrahydroquinoline derivative. Rev. Inst. Med. trop. S. Paulo 14, 59–66 (1972)
Pellegrino, J., Katz, N.: Laboratory evaluation of antischistosomal agents. Ann. N.Y. Acad. Sci. 160, 429–460 (1969)
Pellegrino, J., Katz, N., Dias, E.P.: Experimental chemotherapy of schistosomiasis. VII. Laboratory trials with oxamniquine, a new antischistosomal agent. Rev. Inst. Med. trop. S. Paulo 15 (Suppl. 1), 10–14 (1973)
Pellegrino, J., Katz, N., Oliveira, C.A., Okabe, K.: Rectal biopsy and mucosal curettage in Cebus monkeys experimentally infected with Schistosoma mansoni and Schistosoma japonicum. J. Parasit. 51, 617–621 (1965)
Pellegrino, J., Oliveira, C.A., Faria, J., Cunha, A.S.: New approach to the screening of drugs in experimental schistosomiasis mansoni in mice. Amer. J. trop. Med. Hyg. 11, 201–215 (1962)
Pellegrino, J., Siqueira, A.F.: Técnica para perfusão para colheita de Schistosoma mansoni em cobaias experimentalmente infestadas. Rev. bras. Malar. 8, 589–597 (1956)
Richards, H.C., Foster, R.: A new series of 2-aminomethyltetrahydroquinoline derivatives displaying schistosomicidal activity in rodents and primates. Nature 222, 581–582 (1969)
Rosi, D., Peruzzitti, G., Dennis, E.W., Berberian, D.A., Freele, H., Archer, S.: A new active metabolite of Miracil D. Nature (Lond.) 208, 1005–1006 (1965)
Stohler, H.R., Szente, A.: Tiophene derivatives, a novel group of schistosomicidal compounds. Proc. Third int. Congr. Parasit. 3, 1330 (1974)
Webbe, G., James, C.: A comparison of the susceptibility to praziquantel of Schistosoma haematobium, S. japonicum, S. mansoni and S. mattheei in hamsters. Z. Parasitenk. 52, 169–177 (1977)
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Pellegrino, J., Lima-Costa, F.F., Carlos, M.A. et al. Experimental chemotherapy of schistosomiasis mansoni. Z. F. Parasitenkunde 52, 151–168 (1977). https://doi.org/10.1007/BF00389900
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DOI: https://doi.org/10.1007/BF00389900