Nitrocobinamide, a New Cyanide Antidote That Can Be Administered by Intramuscular Injection
Nitrocobinamide, a New Cyanide Antidote That Can Be Administered by Intramuscular Injection
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DOI：
10.1021/jm501565k
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发表时间：
2015-02-26
影响因子：
7.3
通讯作者：
Boss, Gerry R.
中科院分区：
文献类型：
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作者：
Chan, Adriano;Jiang, Jingjing;Boss, Gerry R.
目前可用的氰化物解毒剂必须在5-10分钟内通过静脉注射给予，使得它们不适合治疗现场的许多人，如可能发生在重大火灾、工业事故或恐怖袭击中的人。这些情况需要一种可以快速给药的药物，例如，通过肌肉注射。我们已经证明，在氰化物中毒的动物模型中，水羟钴氨酰胺是一种有效的氰化物解毒剂，但它在溶液中不稳定，肌肉注射后吸收不良。在这里，我们表明，添加亚硝酸钠的cobinamide产生一个稳定的衍生物（称为nitrocobinamide），抢救氰化物中毒的小鼠和兔子时，肌肉注射。我们还表明，nitrocobinamide的疗效显着增强，通过共同管理硫代硫酸钠（减少总注射体积），我们计算，类似于1.4毫升的nitrocobinamide和硫代硫酸钠应拯救一个人从致命的氰化物暴露。
Currently available cyanide antidotes must be given by intravenous injection over 5-10 min, making them ill-suited for treating many people in the field, as could occur in a major fire, an industrial accident, or a terrorist attack. These scenarios call for a drug that can be given quickly, e.g., by intramuscular injection. We have shown that aquohydroxocobinamide is a potent cyanide antidote in animal models of cyanide poisoning, but it is unstable in solution and poorly absorbed after intramuscular injection. Here we show that adding sodium nitrite to cobinamide yields a stable derivative (referred to as nitrocobinamide) that rescues cyanide-poisoned mice and rabbits when given by intramuscular injection. We also show that the efficacy of nitrocobinamide is markedly enhanced by coadministering sodium thiosulfate (reducing the total injected volume), and we calculate that similar to 1.4 mL each of nitrocobinamide and sodium thiosulfate should rescue a human from a lethal cyanide exposure.