Novel, Orally Effective Cyanide Antidotes

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure.

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical ...

Disulfides as cyanide antidotes: evidence for a new in vivo oxidative pathway for cyanide detoxification.

It is known that cyanide is converted to thiocyanate in the presence of the enzyme rhodanese. The enzyme is activated by sulfur transfer from an appropriate sulfur donor. The activated enzyme then binds cyanide and transfers the sulfur atom to cyanide to form thiocyanate. This project began as an exploration of the ability of disulfides to act as sulfur donors in the rhodanese-mediated detoxifi...

Novel antidotes for target specific oral anticoagulants

Target specific oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) are changing the landscape of anticoagulation. The major drawback is the absence of an effective antidote for severe bleedings and/or prior to procedures. Currently there are a few promising antidotes undergoing clinical trials. This review summarized the latest development in idarucizumab, andexanet alpha and...

XWH - 12 - 2 - 0126 TITLE : Development and Efficacy Testing of Next Generation Cyanide Antidotes

A novel paradigm for assessing efficacies of potential antidotes against neurotoxins in mice.

Historically, antidotal potencies of cyanide antagonists were measured as increases in the experimental LD(50) for cyanide elicited by the antidotes. This required the use of high doses of cyanide following pre-treatment with the putative antidote. Since IACUC guidelines at our institutions strongly discourage LD(50) determinations: we developed a new test paradigm that allowed for maximal surv...