The activity of tricyclic antidepressant drugs against Trypanosoma cruzi.
Imipramine and related derivatives were tested as possible chemotherapeutic agents against Trypanosoma cruzi parasites in vitro. The IC50 values and the lethal concentrations for two cloned stocks of the parasite were determined. 2-Nitrodesmethylimipramine was the most effective compound tested (IC50 = 4-7 microM). Parasites that were able to grow and to complete the intracellular cycle in mammalian cells in the presence of the drug could be selected. Differences in susceptibility to some imipramine analogs between T. cruzi-cloned stocks were found. The study also shows that modification of the imipramine molecule by electron-withdrawing groups greatly enhances its biological activity.
Doyle
P S
PS
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Weinbach
E C
EC
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003470:Culture Media; D007099:Imipramine / Q000031:analogs & derivatives / Q000494:pharmacology*; D015394:Molecular Structure; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
D000929:Antidepressive Agents, Tricyclic; D003470:Culture Media; D007099:Imipramine