Trypanosoma cruzi: Chemotherapeutic effects of clomipramine in mice infected with an isolate obtained from an endemic area

• Published in: Experimental parasitology Vol. 111; no. 2; pp. 80 - 86
• Main Authors: Rivarola, H.W., Bustamante, J.M., Lo Presti, S., Fernández, A.R., Enders, J.E., Gea, S., Fretes, R., Paglini-Oliva, P.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.10.2005; Elsevier
• Subjects: Animals; Antibodies, Protozoan - blood; Antidepressive Agents, Tricyclic - pharmacology; Antidepressive Agents, Tricyclic - therapeutic use; Antigens, Protozoan - immunology; Biological and medical sciences; Calmodulin - antagonists & inhibitors; Chagas Cardiomyopathy - parasitology; Chagas Cardiomyopathy - prevention & control; Chagas Disease - drug therapy; Chagas Disease - parasitology; Chagas Disease - pathology; Chagas’ disease treatment; Clomipramine; Clomipramine - pharmacology; Clomipramine - therapeutic use; Cysteine Endopeptidases - immunology; Drug Resistance; Electrocardiography; Fundamental and applied biological sciences. Psychology; Humans; Immunoglobulin G - blood; Life cycle. Host-agent relationship. Pathogenesis; Male; Mice; Myocardium - metabolism; Myocardium - pathology; Parasitemia - drug therapy; Parasitemia - parasitology; Protozoa; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - metabolism; T. cruzi strains; Trypanocidal Agents - adverse effects; Trypanocidal Agents - pharmacology; Trypanocidal Agents - therapeutic use; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - immunology; Trypanosoma cruzi - pathogenicity; Chagas’ disease treatment; T. cruzi strains; Clomipramine; Kinetoplastida; Protozoa; Protozoal disease; Rodentia; Parasite; Chagas disease; Parasitosis; Trypanosoma cruzi; Infection; Vertebrata; Mammalia; Chagas' disease treatment; Mouse; Trypanosomiasis
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2005.05.005

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 β-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.