Thioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent
phenothiazines to inhibit trypanothione reductase irreversibly. Trypanothione reductase
is an essential enzyme for the survival of Trypanosoma cruzi in the host. Here, we
reviewed the use of this drug for the treatment of T. cruzi experimental infection.
In our laboratory, we have studied the effect of TDZ for the treatment of mice infected
with different strains of T. cruzi and treated in the acute or in the chronic phases
of the experimental infection, using two different schedules: TDZ at a dose of 80
mg/kg/day, for 3 days starting 1h after infection (acute phase), or TDZ 80 mg/kg/day
for 12 days starting 180 days post infection (d.p.i.) (chronic phase). In our experience,
the treatment of infected mice, in the acute or in the chronic phases of the infection,
with TDZ led to a large reduction in the mortality rates and in the cardiac histological
and electrocardiographical abnormalities, and modified the natural evolution of the
experimental infection. These analyses reinforce the importance of treatment in the
chronic phase to decrease, retard or stop the evolution to chagasic myocardiopathy.
Other evidence leading to the use of this drug as a potential chemotherapeutic agent
for Chagas disease treatment is also revised.