Melarsen

Melarsen (211) is active against both early and late stages of African trypanosomiasis. The antimony derivative (212) is used similarly (B-61MI22000, p. 715). 2,4,6-Tripyridyl-l,3,5-triazine forms a purple bis(triazinyl) complex with iron(III) ions which provides a spec-trophotometric method for estimating iron in wines (59MI22001). 

Melarsen was used orally or intravenously but doses were very inaccurate. In fact, it seemed to be less active than tryparsamide and numerous deaths were attributed to this drug [32]. It was abandoned in favor of melarsen oxide (Fig. 5) obtained by reduction of melarsen with sulfur dioxide in the presence of... 

Friedheim EAH (1948) Melarsen oxide in the treatment of human African trypanosomiasis. Ann Trop Med 42 357-363... 

African sleeping sickness Trypanosoma brucei-gambknse, T.b. rhodesiense Suramine, pentamidine, DFMO (for early stage) and tryparsamide, Mel B, Mel W, melarsen sodium, nitrofura-zone (for late stage of the disease with CNS involvement). 

Melarsen sodium (9) This is administered intravenously at a dose of 20 mg/kg given for 8-12 doses separated 5-7 days apart. The toxicity profile of the drug is very much similar to that of tryparsamide [41]. 

Van Schaftingen, E., Opperdoes, F. R. and Hers, H.-G. (1987) Effects of various metabolic conditions of the trivalent arsenical melarsen oxide on the intracellular levels of fructose 2,6-bisphosphate and of glycolytic intermediates in Trypanosoma brucei. Eur. J. Biochem. 166 653-661. 

ANTIPROTOZOAL EFFECTS Melarsoprol is a prodrug that is metabolized rapidly (t j of 30 minutes) to melarsen oxide, the active form. Arsenoxides react avidly and reversibly with sulfhydryl groups and thereby inactivate many enzymes. Melarsoprol reacts with trypanothione to form melarsen oxide-trypanothione adduct, which potently inhibits trypanothione reductase. Both the sequestering of trypanothione and the inhibition of trypanothione reductase are expected to have lethal consequences to the cell, but this remains unproven. 

Melarsoprol is administered IV in multiple doses and multiple sessions. Its major metabolite in humans is the lipophilic melarsen oxide, which can penetrate into the CNS. This metabolite apparently is responsible for the protein-binding characteristic for melarsoprol. 

---