[1] It is specifically used for second-stage disease caused by Trypanosoma brucei rhodesiense when the central nervous system is involved.

[4] Common side effects include brain dysfunction, numbness, rashes, and kidney and liver problems.

[2] About 1–5% of people die during treatment, although this is tolerated due to sleeping sickness itself having a practically 100% mortality rate when untreated.

[12] Melarsoprol is a prodrug, a complex of melarsen oxide (a melamine derivative of phenylarsonous acid) with dimercaprol (also known as British anti-Lewisite, or BAL).

It is metabolized to melarsen oxide in the body, which then acts by irreversibly binding to sulfhydryl groups on the enzyme pyruvate kinase, thus disrupting energy production in the parasite.

The inability to distinguish between the host's and the parasite's pyruvate kinase renders this drug highly toxic, with many side effects.

[citation needed] Melarsen oxide also reacts with trypanothione (a spermidine-glutathione adduct that replaces glutathione in trypanosomes).

It forms a melarsen oxide-trypanothione adduct (Mel T) that competitively inhibits trypanothione reductase, effectively killing the protist.

[citation needed] Melarsoprol used for the treatment of African trypanosomiasis with CNS involvement is given under a complicated dosing schedule.

[3] As a toxic organic compound of arsenic, melarsoprol is a dangerous treatment that is typically only administered by injection under the supervision of a licensed physician.

It is known to cause a range of side effects including convulsions, fever, loss of consciousness, rashes, bloody stools, nausea and vomiting.

An evaluation of the cerebrospinal fluid via a lumbar puncture is also used to determine an individual's white blood count and level of protein.

Continuous cerebrospinal fluid evaluation should be repeated every six months for at least three years in individuals that have undergone melarsoprol treatment.

The World Health Organization suggests that treatment be deferred until immediately after delivery since the effects of the medication on the developing fetus have not yet been established.

[16] Melarsoprol was used to treat a patient with second-stage African trypanosomiasis on season 1 episode 7 "Fidelity" of the medical drama House MD.