We have also developed a unique mouse model-that minimizes the use of large numbers of animals~for assessing the toxicity of sub-lethal doses of cyanide, which is highly amenable for evaluating the antidotal efficacy of our compounds. The rationale here is to provide this enzyme with its natural substrate directly, thereby by-passing the necessity for generating it endogenously from the transamination of L-cysteine, a sulfhydryl amino acid known to be less abundant in tissues. We have recently developed (unpublished) a series of prototype cyanide antidotes that release the substrate for the enzyme, 3-mercaptopyruvate sulfurtransferase (3-MPST) in vivo, thereby providing a viable alternative method for detoxifying cyanide by utilizing this ubiquitous cellular enzyme to convert cyanide to the non-toxic thiocyanate. These goals have not yet been achieved to date, and the present treatment modalities are unsuitable in a military setting, or in the event of actual use of cyanide as a threat agent on a large scale against the civilian population. A recent perspective article on cyanide, authored by experts at the USAMRICD, pointed out that in severe cyanide poisonings, rapid intervention is the key, and treatments require a """"""""three minute solution"""""""", akin to the nerve agent antidote kit.3 The availability of non-toxic agents that could be taken prophylactically by military personnel on threatened exposure or by first responders to a cyanide emergency, also represents an ideal requirement. However, these agents are generally not only slow acting, but have potential for toxicity and serious complications if not used properly. In recent years, this has been supplemented with the volatile amyl nitrite given nasally for its vasodilatory effect. for over 30 years have been the combination of sodium nitrite and sodium thiosulfate, both administered intravenously in timely sequence. Although different nations have variable preferences for specific antidotes against cyanide poisoning, the antidotes of choice in the U.S.
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