Association of oxamniquine praziquantel and clonazepam in experimental Schistosomiasis mansoni.
The antischistosomal activity of clonazepam, when administered alone or in association with oxamniquine and praziquantel, was experimentally evaluated in mice infected with Schistosoma mansoni. The animals were treated 45 days post-infection with a single dose, by oral route, according to three treatment schedules: clonazepam 25 mg/kg and sacrificed 15 min, 1h or 4 h after treatment; clonazepam 1.0, 2.5 or 10.0 mg/kg and sacrificed 15 days post-treatment or with the dose of 10 mg/kg in association with oxamniquine 50 mg/kg or praziquantel 200 mg/kg, single dose, orally, every schedule with a control group. The efficacy of the drugs in vivo was assessed by means of worm counts and their distribution in mesentery and liver, mortality and oogram changes. In the chemotherapeutic schedules used, clonazepam did not present antischistosomal activity and the result of the association of this drug with oxamniquine or praziquantel was not significantly different from the one obtained when these two last drugs were administered alone. In the in vitro experiments, the worms exposed to 0.6 mg/mL clonazepam remained motionless throughout the 8-day-period of observation, without egg-laying, whereas the worms of the control group showed normal movements, egg-laying and hatching of miracidia on the last day of observation. The results obtained in the present study confirm the action of clonazepam on S. mansoni adult worm, in vitro, causing total paralysis of males and females. However, no additive or synergistic effects were observed when clonazepam were used in association with oxamniquine or praziquantel.
Araujo
Neusa
N
Laboratório de Esquistossomose, Instituto René Rachou-Fiocruz, Belo Horizonte, MG, Brasil. araujon@cpqrr.fiocruz.br
Mattos
Ana Carolina Alves de
AC
Coelho
Paulo Marcos Zech
PM
Katz
Naftale
N
D000818:Animals; D002998:Clonazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005260:Female; D008099:Liver / Q000469:parasitology; D008297:Male; D008643:Mesentery / Q000469:parasitology; D051379:Mice; D010073:Oxamniquine / Q000008:administration & dosage / Q000494:pharmacology; D011223:Praziquantel / Q000008:administration & dosage / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000187:drug effects*; D012555:Schistosomiasis mansoni / Q000188:drug therapy*; D012556:Schistosomicides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D012556:Schistosomicides; D010073:Oxamniquine; D002998:Clonazepam; D011223:Praziquantel