Clomipramine therapy during the chronic phase of experimental Chagas disease.

FAURO ROMINA; BAZÁN CAROLINA; MICUCCI LORENA; STRAUSS MARIANA; LO PRESTI SILVINA; BÁEZ ALEJANDRA; TRIQUELL FERNANDA; CREMONEZZI DAVID; PAGLINI PATRICIA; RIVAROLA WALTER

Río de Janeiro, Brasil

Simposio; International simposium on the Centennial of the Discovery of Chagas Disease.; 2009

Fundación Oswaldo Cruz

Chagas disease is a very complex zoonosis and a permanent threat that affects almost a fourth of the population of Latin America. Chagasic patients have been detected throughout Mexico, Central and South America, with very variable clinical manifestations and epidemiological characteristics in the different endemic areas. Unfortunately, the specific treatments currently available for this parasitic disease, nifurtimox and benznidazole, have limited efficiency and frequent undesirable side effects. The identification of metabolic pathways and the finding of new molecular targets in the parasite are helpful for developing more effective trypanocidal drugs. These molecular targets must be parasite-specific, and their interaction with the trypanocidal drug should not produce any metabolic alteration in the mammalian host such as trypanothione reductase (TR) and hypoxanthine-guanine ribosyltransferase (HGRT), both of which fulfill a vital function in the parasite. Clomipramine is a tricyclic drug used in psychiatric treatment which has been found to disable TR. Allopurinol, in turn, disables the synthesis of guanylic acid and the adenylic pathway of HGRT. In our laboratory we demonstrated that allopurinol and clomipramine used for the treatment of acute Trypanosoma cruzi infection in mice prevented it evolving into chronic chagasic cardiopathy. Taking into account the high toxicity of the drugs commonly used for Chagas disease treatment, the possible existence of resistant parasite strains and the coexistence of more than one strain in the same patient, it is possible that the simultaneous administration of two or more drugs with different mechanisms of action, different specificities against parasite strains and different targets, and with fewer adverse side effects, could optimize the treatment The aim of the present work was to evaluate the effect of the association of clomipramine and allopurinol for the treatment of experimental Chagas disease in the acute stage.