Investigators from the University of Minnesota are reporting in the latest issue of Journal of Medicinal Chemistry that their compound called sulfanagen was found to be twice as effective as a standard cyanide antidote when orally administered to lab mice. This novel potential treatment is based on 3-mercaptopyruvate (3-MP), a substrate for the enzyme 3-mercaptopyruvate/cyanide sulfurtransferase (3-MPST), an enzyme that converts naturally occurring (in pitted fruits, grasses and other foods) cyanide to the nontoxic thiocyanate. Here’s the reaction that is thought to be catalyzed by sulfanagen through sulfurtransferase :
pyruvate + thiocyanate
From the press statement by the University of Minnesota:
Current cyanide antidotes work slowly and are ineffective when administered after a certain point, said Steven Patterson, Ph.D., principal investigator and associate director of the University of the Minnesota Center for Drug Design.
Patterson is developing an antidote that was discovered by retired University of Minnesota Professor Herbert Nagasawa. This antidote works in less than three minutes — meeting the United States Department of Defense “three minute solution” standard. The research will be featured in the Dec. 27, 2007 issue of the Journal of Medicinal Chemistry.
“It’s much, much faster than current antidotes,” Patterson said. “The antidote is also effective over a wider time window. Giving emergency responders more time is important because it’s not likely that someone will be exposed to cyanide near a paramedic.”
The antidote was tested on animals and has been exceptionally effective, Patterson said. Researchers hope to begin human clinical trials during the next three years.
The antidote is also unique because it can be taken orally (current antidotes must be given intravenously) and may be administered up to an hour prior to cyanide exposure.
Cyanide is a rapid acting toxin that inhibits cellular respiration — it prevents the body from using oxygen. This means it rapidly shuts down many of the fundamental biochemical processes the body needs to survive. Symptoms of acute cyanide poisoning include headache, vertigo, lack of motor coordination, weak pulse, abnormal heartbeat, vomiting, stupor, convulsions, coma, and even death.
When released in an enclosed area, cyanide can be particularly deadly and impact a victim very quickly. Survivors of cyanide poisoning are also at risk of short-term memory loss and development of a Parkinson’s-like syndrome.
Press release: U of M researchers discover fast-acting cyanide antidote …
The abstract: Novel, orally effective cyanide antidotes. J Med Chem. 2007 Dec 27;50(26):6462-4.
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