The importance of 2,3-dimercaptopropinol (British anti-lewisite, BAL) in the trypanocidal activity of topical melarsoprol.
Both melarsomine dichlorhydrate (mel Cy, Cymelarsan) and melarsen oxide can be dissolved in dimethylsulfoxide and converted into a gel by the addition of hydroxypropylcellulose. When Trypanosoma brucei brucei-infected mice are treated topically with these gels the circulating trypanosomes are rapidly cleared from the circulation but the infections relapse soon after the last application. However, when these two compounds are allowed to react with 2,3-dimercaptopropinol (British anti-lewisite, BAL) and form "melarsoprol" their efficacy, especially in the case of mel Cy, is restored to that of commercial melarsoprol (Arsobal) and trypanosomes in the central nervous system (CNS) can be eliminated. This would indicate that the dimercaptopropinol portion of the molecule does not act solely as an "antidote" to arsenic toxicity, but also plays an important role in the absorption of melarsoprol through the skin and/or blood-brain barrier into the CNS and/or into the trypanosome.
Jennings
F W
FW
Department of Veterinary Parasitology, University of Glasgow, UK.
Atouguia
J M
JM
Murray
M
M
D000287:Administration, Topical; D000818:Animals; D001152:Arsenicals / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004112:Dimercaprol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D005782:Gels; D008549:Melarsoprol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D001152:Arsenicals; D004338:Drug Combinations; D005782:Gels; D014344:Trypanocidal Agents; D004112:Dimercaprol; C044719:melarsen oxide; C062789:melaminylthioarsenate; D008549:Melarsoprol