A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios. Presently used CN therapies include: methemoglobin/NO generators ( e.g., sodium nitrite, amyl nitrite, and dimethyl aminophenol), sulfur donors ( e.g., sodium thiosulfate and glutathione), and direct binding agents. The discovery of NO’s ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites. Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide (NO) in the body. These fundamental studies led to a variety of antidotes, including indirect CN binders that generate methemoglobin, direct CN binders such as hydroxocobalamin, and sulfur donors that convert CN to the less toxic thiocyanate.

The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929. It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent. CN has been a part of plant defense mechanisms for millions of years. This paper reviews milestones in antidotal therapies for cyanide (CN) spanning early remedies, current antidotal systems and research towards next generation therapies.

Cyanide poisoning antidote mechanism