Thioridazine treatment modifies the evolution of Trypanosoma cruzi infection in mice

• Published in: Annals of tropical medicine and parasitology Vol. 93; no. 7; pp. 695 - 702
• Main Authors: Rivarola, H. W., Fernández, A. R., Enders, J. E., Fretes, R., Gea, S., Suligoy, M., Palma, J. A., Paglini-Oliva, P.
• Format: Journal Article
• Language: English
• Published: Leeds Taylor & Francis 01.10.1999; Maney Publishing
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Biological and medical sciences; Chagas Disease - drug therapy; Chagas Disease - enzymology; Drug Evaluation, Preclinical; Medical sciences; Mice; Pharmacology. Drug treatments; Thioridazine - administration & dosage; Thioridazine - therapeutic use; Tropical medicine; Trypanocidal Agents - administration & dosage; Trypanocidal Agents - therapeutic use; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - enzymology; South America; Argentina; America; Kinetoplastida; Protozoa; Modification; Protozoal disease; Rodentia; Oral administration; Phenothiazine derivatives; Parasitosis; Experimental study; Route of administration; Trypanosoma cruzi; Infection; Vertebrata; Mammalia; Thioridazine; Mouse; Animal; Parasiticid; Evolution; Mechanism of action; Trypanosomiasis
• ISSN: 0003-4983; 1364-8594
• DOI: 10.1080/00034983.1999.11813474

Thioridazine, a tricyclic drug, is known to have a direct effect on Trypanosoma cruzi, disrupting the parasites' mitochondria and kinetoplasts. In the present study, the drug was used orally, at 80 mg/kg.day for 3 days, to treat mice inoculated with low numbers of T. cruzi. The drug caused no apparent toxicity in the host. It cleared trypomastigotes from the bloodstream, prevented the histological and functional alterations of the heart normally observed in the chronic phase of the experimental disease, and greatly reduced the mortality rate compared with that in untreated, infected controls. When checked 135 days post-infection, the density of cardiac β receptors and the cardiac histology of the treated mice were indistinguishable from those of uninfected, untreated controls. The drug is already used to treat humans, as a neuroleptic drug. It appears to be able to prevent acute infection with T. cruzi evolving into chronic disease, at least in mice, and may be a useful base from which to design new agents for the treatment of Chagas disease.