Arsenic and antimonial compounds have been used since ancient times. They form stable complexes with sulfur compounds and probably exert their biological effects by binding to sulfhydryl groups. They are toxic to the host as well as to the parasite and have their greatest impact on cells that are most metabolically active such as neuronal, renal tubular, intestinal epithelial, and bone marrow stem cells. Their differential toxicity and therapeu-tic value are due to enhanced uptake by the parasite and its intense metabolic activity. Only one trivalent arsenical, melarsoprol* (Mel B), is now widely used. It is capable of penetrating the blood–brain barrier and is effective in all stages of trypanosomiasis. Because of its toxicity, it is employed only when less toxic agents have failed or the central nervous system is involved. The recently introduced less toxic trypanocides that penetrate the blood–brain barrier may soon replace this drug.
Antimonial agents are now restricted to the management of leishmanial infections. Two pentavalent compounds, sodium stibogluconate* (Pentostam) and meglumine antimoniate†(Glucantime), are used for all forms of leishmaniasis. In disseminated disease, prolonged therapy is usually required and relapses often occur. In localized cutaneous leishmaniasis, cure is usually achieved with a relatively brief course. Toxic side effects are similar to those of the arsenicals.