The potentiation of arsenicals with difluoromethylornithine (DFMO): experimental studies in murine trypanosomiasis.
The efficacy of melarsoprol in the treatment of chronic T. b. brucei infections in mice can be increased approximately 5 times if DL-a-difluoromethylornithine (DFMO) is given in the drinking water at the same time. A more detailed study substantiated the concept that a reduction in both the size and the rate of replacement of the trypanothione pool are the key factors in the efficiency of melarsoprol chemotherapy. It was therefore best to give the melarsoprol towards the end of the DFMO regimen, and as a guanylhydrazone (TBG) also blocks trypanothione (polyamine) biosynthesis, if TBG/DFMO are given together the treatment period can be reduced to 8 days. The antimony compound, sodium stibogluconate (Pentostam), used in combination with DFMO can also cure these infections and demonstrates that arsenic could be substituted by antimony in the treatment of CNS infections.
Jennings
F W
FW
Department of Veterinary Parasitology, University of Glasgow.
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage / Q000627:therapeutic use; D001152:Arsenicals / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000518:Eflornithine / Q000008:administration & dosage* / Q000627:therapeutic use; D008549:Melarsoprol / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D008935:Mitoguazone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D001152:Arsenicals; C040056:1,3,5-triacetylbenzene tris(guanylhydrazone); D008935:Mitoguazone; D000967:Antimony Sodium Gluconate; D008549:Melarsoprol; D000518:Eflornithine