Chemotherapy of CNS-trypanosomiasis: the combined use of the arsenicals and nitro-compounds.
In trypanosomiasis chemotherapy the main mode of action of the nitro-compounds, including the 5-nitroimidazoles or nitrofurans (nifurtimox) is to increase the oxidative stress on the organism either directly by the production of peroxides or indirectly by "futile redox cycling". If this is the case, then these nitro-compounds and the arsenicals should act in combination on the trypanothione oxidation-reduction reaction of the trypanosome. In this paper this has been demonstrated to occur with all those nitro-compounds which have exhibited reasonable trypanocidal action in monotherapy or other combination chemotherapeutic regimens. A major advantage is the short treatment period of approximately 5 days. Pretreatment with a single dose of suramin increased the efficacy of the nitroimidazole-arsenical combination.
Jennings
F W
FW
Department of Veterinary Parasitology, University of Glasgow.
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D001152:Arsenicals / Q000494:pharmacology / Q000627:therapeutic use*; D001927:Brain Diseases / Q000188:drug therapy*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007654:Ketoconazole / Q000494:pharmacology / Q000627:therapeutic use; D008795:Metronidazole / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009547:Nifurtimox / Q000494:pharmacology / Q000627:therapeutic use; D009574:Nitro Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D009593:Nitroimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D010084:Oxidation-Reduction; D013498:Suramin / Q000494:pharmacology / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D000981:Antiprotozoal Agents; D001152:Arsenicals; D009574:Nitro Compounds; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D008795:Metronidazole; C038307:fexinidazole; C022191:MK 436; C015980:melarsonic acid; C034473:satranidazole; C039889:L 611744; D013498:Suramin; C039890:L 634549; D009547:Nifurtimox; D007654:Ketoconazole