Treatment with suramin and 2-substituted 5-nitroimidazoles of chronic murine Trypanosoma brucei infections with central nervous system involvement.
Mice infected with either of two isolates of Trypanosoma brucei, GVR 23/1 or GVR 35/1, develop a chronic infection in which trypanosomes are localized in the central nervous system. These infected mice were used to evaluate the efficacy of a combination drug treatment comprising suramin and one of three 2-substituted 5-nitroimidazoles. None of the three 5-nitroimidazoles tested alone, cured mice when administered 21 days after infection. However, it was found that T. brucei GVR 23/1 infections could be cured by a single dose of 20 mg/kg suramin followed by a single dose of 80 mg/kg L611,744 [3a,4,5,6,7,8,9,9a-octahydro-3-(1-methyl-5-nitroimidazol-2yl)cycloocta(D) isoxazole]. The single dose of 20 mg/kg suramin had to be followed by four doses of 80 mg/kg L611,744 to cure mice infected with another stabilate, T. brucei GVR 35/1. A single dose of 20 mg/kg suramin followed either by four doses of 250 mg/kg MK 436 [3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5nitro-1H-imidazol-2-yl)-1, 2-benzisoxazole] or four doses of 70 mg/kg of a dihydroxy analogue of MK 436 [cis-3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1, 2-benzisoxazole-6,7-diol] also permanently cured all T. brucei GVR 35/1.
D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D002417:Cattle; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000469:parasitology; D004359:Drug Therapy, Combination; D005260:Female; D051379:Mice; D009593:Nitroimidazoles / Q000627:therapeutic use*; D013498:Suramin / Q000627:therapeutic use*; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D000981:Antiprotozoal Agents; D009593:Nitroimidazoles; C022191:MK 436; C039889:L 611744; D013498:Suramin; C039890:L 634549