Melarsoprol is a trivalent arsenical made by coupling melarsen oxide to 2, 3-dimercaptopropinol, also known as British anti-Lewisite.
Melarsoprol is the mainstay of therapy in late-stage cases of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense sleeping sickness.
Melarsoprol can interact with thiol groups of several different proteins but interactions between melarsoprol and the parasite specific glutathione-spermidine conjugate trypanothione might be of more physiological relevance.
Wild-type trypanosomes have two adenosine transporters, P1 and P2, but only P2 transports melanophenyl arsenicals. Resistant parasites lack the P2 transporter.
Melarsoprol is transformed into active metabolites; initially melarsen oxide is the active drug. Melarsen oxide has a half-life of 3.8 hours. Melarsoprol is excreted mostly through the GI tract, but active metabolites are found in the urine.
Gambian trypanosomiasis: 2.2 mg/kg daily for 10 days. See text for alternative requirements.
Rhodesian trypanosomiasis: after 2 or 3 doses of suramin as pre-treatment, a reasonable strategy would be: 0.36 mg/kg on day 1, 0.72 (day 2), 1.1 (day 3), 1.4 (day 10), 1.8 (days 11, 12), 2.2 (day 19), 2.9 (day 20) and 3.6 mg/kg (up to 180 mg) on days 21, 28, 29 and 30.