Pre-Clinical Study for Fast Acting Cyanide Antidote

Overview


Cyanide is a rapid acting toxin that inhibits cellular respiration, rapidly shutting down many of the fundamental biochemical processes the body needs to survive by preventing the body from using oxygen. 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. A fast-acting antidote to cyanide poisoning has the potential to save the lives of those who are exposed to the toxin, including firefighters, industrial workers, and victims of terrorist attack. In severe cyanide poisonings, rapid intervention is the key.


Robert Vince, Herbert Nagasawa and Steve Patterson

Recently the researchers from the University of Minnesota Center for Drug Design and the Minneapolis Veterans Affairs Medical Center have discovered a fast acting antidote based on mechanisms used by the body to detoxify small amounts of cyanide that occur naturally in pitted fruits, some grasses, and other foods. The new antidote takes advantage of this natural detoxification pathway by converting cyanide to non-toxic thiocyanate. Independently, the team at UCSD has also discovered another rapidly acting antidote that works by sequestering cyanide. The resulting complex is then safely removed from the body in urine.

At the University of California Irvine (UCI), the team has developed an effective and fast method for assessing cyanide toxicity. Using this non-invasive optical method, the team at UCI can rapidly access the effects of cyanide and efficacy of novel antidotes. In addition, the team at UCI has developed a new formulations and administration methods that provide for faster and easier delivery of antidotes to victims of cyanide poisoning.


This project is a collaboration between researchers from the Center for Drug Design, University of Minnesota, the Minneapolis Veterans Affairs (VA) Medical Center (MN, USA), The University of California San Diego (UCSD), and the University of California Irvine. When combined in animal models, the Minnesota and UCSD antidotes work synergistically against cyanide poisoning and are being developed as combination therapy by the above teams. The resulting antidote works prophylactically to prevent or limit toxicity associated from exposure to cyanide. Our antidotes are faster acting and are safer than existing antidotes. 
Sponsored by NIH grant: 1U54NS063718-01



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