Chemotherapy of trypanosomiasis: the use of guanylhydrazone compounds in the treatment of experimental murine trypanosomiasis

Jennings, F.W.; Ulrich, P.; Cerami, A.

Tropical Medicine and Parasitology Official Organ of Deutsche Tropenmedizinische Gesellschaft and of Deutsche Gesellschaft für Technische Zusammenarbeit 38(3): 181-186

1987


ISSN/ISBN: 0177-2392
PMID: 3124253
Document Number: 299978
The efficacy of 1,3,5-triacetylbenzene tris(guanylhydrazone) trihydrochloride (TBG) in the treatment of early and late stage infections of Trypanosoma brucei in mice was investigated. Successful treatment on day 3 pi could be achieved by doses of 2 x 2.5 mg/kg. When treatment was delayed to 21 days pi, however, a single dose of suramin (20 mg/kg) followed by TBG (3 days later) at 1 x 10 mg/kg twice daily for 4 days were required to cure all animals. High rates of cure were also obtained in mice given 1 x 20 mg/kg suramin and 4 x 15 gm/kg TBG, or difluoromethylornithine (DFMO) 2% solution in drinking water for 14 days followed by TBG at 4 x 15 mg/kg or 1 x 10 mg/kg twice daily for 4 days. Other guanylhydrazone derivatives were investigated for the treatment of chronic T. brucei infections, but failed to given any permanent cures at the limited dose levels used ( 2 x 20 mg/kg). The guanylhydrazone derivative 1,3,5-triacetylbenzene tris(guanylhydrazone) trihydrochloride was effective against early (day 3) murine infections with Trypanosoma brucei GVR 35/2 at doses of 2 x 2.5 mg/kg. Later infections (day 21) required the addition of suramin or DMFO for cure, and the dose of the derivative needed to be raised to near the toxic level (20 mg/kg). Preliminary studies indicated that the derivative was also active against early infections with T. congolense and T. evansi in mice.

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