Oral Cyanide Antidote

Firefighters are at risk of cyanide poisoning because the toxic ion is produced during residential and industrial fires. Current drug treatments require intravenous injections, but now Herbert T. Nagasawa and coworkers at the Center for Drug Design at the University of Minnesota and the Department of Veterans Affairs Medical Center, Minneapolis, report oral cyanide antidotes (J. Med. Chem., DOI: 10.1021/jm7011497). Cyanide (CN^-) is detoxified in the body by conversion to the less toxic thiocyanate (SCN^-). Nagasawa and coworkers' antidotes target a more widely distributed enzyme—3-mercaptopyruvate sulfurtransferase—than does the IV treatment. The enzyme uses 3-mercaptopyruvate (3-MP, shown) as the source of sulfur to convert CN^- to SCN^-. Because 3-MP is chemically unstable, the researchers designed five prodrugs that decompose to release 3-MP in the body. When administered orally to mice, these drugs were effective against toxic, but nonlethal, doses of cyanide, even when administered prophylactically up to an hour before exposure.