Trypanosoma cruzi: chemotherapeutic effects of clomipramine in mice infected with an isolate obtained from an endemic area.
The susceptibility of Trypanosoma cruzi strains to nifurtimox and benznidazole has been investigated and resistant strains have been described. Some tricyclic drugs are lethal for trypomastigote and epimastigote forms of T. cruzi (Tulahuen strain) and prevent the disease in mice. We investigated whether clomipramine, a tricyclic antidepressant drug with anti-trypanothione reductase and anti-calmodulin effects, could be effective in treating Albino Swiss mice infected with trypomastigotes of a new T. cruzi isolate from a chronic patient from an endemic area of Argentina in two different treatment schedules. Both treatment schedules were effective in reducing electrocardiographic changes and preventing myocardial structural damage. The cardiac beta-receptors low affinity was compensated for by an increment in their density. This probably maintained cardiac function since 70% of the mice survived for more than 2 years even though anti-cruzipain titers remained high. These results demonstrate that clomipramine, clinically used as a neuroleptic, could be a promising trypanocidal agent for the treatment of Chagas' disease.
Rivarola
H W
HW
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, 5000 Córdoba, Argentina. hrivarola@hotmail.com
Bustamante
J M
JM
Lo Presti
S
S
Fernández
A R
AR
Enders
J E
JE
Gea
S
S
Fretes
R
R
Paglini-Oliva
P
P
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology / Q000627:therapeutic use; D000953:Antigens, Protozoan / Q000276:immunology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002598:Chagas Cardiomyopathy / Q000469:parasitology / Q000517:prevention & control; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D002997:Clomipramine / Q000494:pharmacology / Q000627:therapeutic use*; D003546:Cysteine Endopeptidases / Q000276:immunology; D004351:Drug Resistance; D004562:Electrocardiography; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D015800:Protozoan Proteins; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D014344:Trypanocidal Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity
D000913:Antibodies, Protozoan; D000929:Antidepressive Agents, Tricyclic; D000953:Antigens, Protozoan; D002147:Calmodulin; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D011943:Receptors, Adrenergic, beta; D014344:Trypanocidal Agents; D003546:Cysteine Endopeptidases; C063214:cruzipain; D002997:Clomipramine