antiprotozoal drug formerly used in the treatment of late-stage African trypanosomiasis ( sleeping sickness). Melarsoprol is an organoarsenic compound that was discovered in 1949. Its ability to cross the blood-brain barrier made it particularly effective against late-stage Gambian (or West African) sleeping sickness, which is characterized by entry of the protozoan Trypanosoma brucei gambiense into the central nervous system (nervous system, human). Melarsoprol was also used effectively against late-stage Rhodesian (or East African) sleeping sickness, caused by T. brucei rhodesiense. Though melarsoprol's mechanism of action was never entirely understood, scientists suspected that the drug killed trypanosomes by inhibiting a fundamental pathway of energy metabolism.

Melarsoprol was extremely toxic to humans, causing life-threatening encephalopathy (diffuse brain disease) in about 5–10 percent of patients treated with the drug. In the early 2000s it was found that melarsoprol-resistant trypanosomes accounted for treatment failure in nearly 20 percent of patients in central Africa. Shortly thereafter melarsoprol was supplanted by eflornithine in the treatment of late-stage Gambian sleeping sickness.