The use of 2-substituted 5-nitroimidazoles in the treatment of chronic murine Trypanosoma brucei infections with central nervous system involvement.
Chronic infections of Trypanosoma brucei GVR 35/2 in mice, normally relapse after conventional chemotherapy because infective trypanosomes in the brain escape the action of the drug and are able to multiply and eventually re-establish a parasitaemia. However, if treatment consists of a single dose of 1 x 20 mg/kg suramin followed 3 or 4 days later by a 2-substituted 5-nitroimidazole, given intraperitoneally, either as a single dose or as a course of daily injections, relapses rarely occur and the majority of the mice are permanently cured. The minimum effective levels for the three 5-nitroimidazole compounds (Merck Sharp and Dohme, Rahway, NJ, USA) were two doses of 10 mg/kg of L611,744; four doses of 10 mg/kg of MK 436; and three doses of 10 mg/kg of L634,549. Generally it was more effective to divide a given total dose into two or more daily doses, rather than to give the 4-nitroimidazole as a single treatment. The effective dose levels are low enough to be of practical significance and, if the 5-nitroimidazoles were ever licensed for humans, might well prove to be an alternative to melarsoprol treatment for the elimination of trypanosomes from the central nervous system.
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000469:parasitology*; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D012376:Rodent Diseases / Q000188:drug therapy* / Q000469:parasitology; D013498:Suramin / Q000008:administration & dosage / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014346:Trypanosoma brucei brucei / Q000302:isolation & purification; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*
D000981:Antiprotozoal Agents; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C022191:MK 436; C039889:L 611744; D013498:Suramin; C039890:L 634549