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Exp Parasitol ; 111(2): 80-6, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16085036

RESUMO

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.


Assuntos
Doença de Chagas/tratamento farmacológico , Clomipramina/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Animais , Anticorpos Antiprotozoários/sangue , Antidepressivos Tricíclicos/farmacologia , Antidepressivos Tricíclicos/uso terapêutico , Antígenos de Protozoários/imunologia , Calmodulina/antagonistas & inibidores , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/prevenção & controle , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Clomipramina/farmacologia , Cisteína Endopeptidases/imunologia , Resistência a Medicamentos , Eletrocardiografia , Humanos , Imunoglobulina G/sangue , Masculino , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Proteínas de Protozoários , Receptores Adrenérgicos beta/efeitos dos fármacos , Receptores Adrenérgicos beta/metabolismo , Tripanossomicidas/efeitos adversos , Tripanossomicidas/farmacologia , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/patogenicidade
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