Toward a better cyanide antidote for terrorist attacks and other mass casualty events

Jan 30, 2013

In an advance toward closing a major gap in defenses against terrorist attacks and other mass casualty events, scientists are reporting discovery of a promising substance that could be the basis for development of a better antidote for cyanide poisoning. Their report, which describes a potential antidote that could be self-administered, much like the medication delivered by allergy injection pens, appears in ACS' Journal of Medicinal Chemistry.

Steven E. Patterson, Ph.D., and colleagues at the University of Minnesota Center for Drug Design explain that the only existing antidotes for cyanide—recognized as a high-risk substance for potential use by terrorists—must be administered by intravenous infusion. That procedure requires highly trained paramedical personnel and takes time. Cyanide, however, is a fast-acting poison. In a situation involving , only a limited number of victims could be saved. Patterson's team thus sought an antidote that could be administered by intra-muscular (IM) injection, a simpler procedure that could be administered rapidly to a large number of victims or even be self-administered.

Their report describes discovery of a substance, sulfanegen TEA, "which should be amenable for development as an IM injectable antidote suitable for treatment of cyanide victims in a mass casualty setting. Further development, including efficacy in lethal cyanide animal models, will be reported at a later date."

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More information: "Cyanide Antidotes for Mass Casualties: Water-Soluble Salts of the Dithiane (Sulfanegen) from 3- Mercaptopyruvate for Intramuscular Administration", J. Med. Chem., Just Accepted Manuscript, DOI: 10.1021/jm301633x

Abstract
Current cyanide antidotes are all administered by IV infusion, a suboptimal procedure in a mass casualty setting. Therefore, in a cyanide disaster from a chemical accident or an act of terrorism, intramuscular (IM) injectable antidotes would be more appropriate. It has become clear that our lead cyanide antidote, viz., sulfanegen sodium, is insufficiently water-soluble for the IM mode of administration. We now report the discovery of the highly water-soluble sulfanegen triethanolamine salt, with greater than a 4-fold increase in solubility and increase in potency compared to the parent sulfanegen sodium, thus offering a promising lead for development as an IM injectable cyanide antidote.

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