考比酰胺与磺胺乙胺联合使用在氰化物中毒的小鼠模型中具有高度疗效。
The combination of cobinamide and sulfanegen is highly effective in mouse models of cyanide poisoning.
机构信息
Department of Medicine, University of California-San Diego, 9500 Gilman Dr., La Jolla,CA 92093-0652, USA.
出版信息
Clin Toxicol (Phila). 2011 Jun;49(5):366-73. doi: 10.3109/15563650.2011.584879.
CONTEXT
Cyanide is a component of smoke in residential and industrial fires, and accidental exposure to cyanide occurs in a variety of industries. Moreover, cyanide has the potential to be used by terrorists, particularly in a closed space such as an airport or train station. Current therapies for cyanide poisoning must be given by intravenous administration, limiting their use in treating mass casualties.
OBJECTIVE
We are developing two new cyanide antidotes--cobinamide, a vitamin B(12) analog, and sulfanegen, a 3-mercaptopyruvate prodrug. Both drugs can be given by intramuscular administration, and therefore could be used to treat a large number of people quickly. We now asked if the two drugs would have an augmented effect when combined.
MATERIALS AND METHODS
We used a non-lethal and two different lethal models of cyanide poisoning in mice. The non-lethal model assesses neurologic recovery by quantitatively evaluating the innate righting reflex time of a mouse. The two lethal models are a cyanide injection and a cyanide inhalation model.
RESULTS
We found that the two drugs are at least additive when used together in both the non-lethal and lethal models: at doses where all animals died with either drug alone, the combination yielded 80 and 40% survival in the injection and inhalation models, respectively. Similarly, drug doses that yielded 40% survival with either drug alone, yielded 80 and 100% survival in the injection and inhalation models, respectively. As part of the inhalation model, we developed a new paradigm in which animals are exposed to cyanide gas, injected intramuscularly with an antidote, and then re-exposed to cyanide gas. This simulates cyanide exposure of a large number of people in a closed space, because people would remain exposed to cyanide, even after receiving an antidote.
CONCLUSION
The combination of cobinamide and sulfanegen shows great promise as a new approach to treating cyanide poisoning.
背景
氰化物是住宅和工业火灾烟雾的成分，在各种工业中都有意外接触氰化物的情况。此外，氰化物有可能被恐怖分子使用，特别是在机场或火车站等封闭空间。目前治疗氰化物中毒的疗法必须通过静脉给药，这限制了它们在治疗大量伤亡人员中的应用。
目的
我们正在开发两种新的氰化物解毒剂 - 钴胺酰胺，维生素 B12 类似物，和磺酸钠，3-巯基丙酮酸前药。这两种药物都可以通过肌肉内给药，因此可以快速用于治疗大量人群。我们现在想知道这两种药物结合使用是否会产生增强作用。
材料和方法
我们使用了一种非致命的和两种不同致命的氰化物中毒小鼠模型。非致命模型通过定量评估小鼠的固有翻身反射时间来评估神经恢复。两种致命模型是氰化物注射和氰化物吸入模型。
结果
我们发现，这两种药物在非致命和致命模型中联合使用时至少具有相加作用：在单独使用任何一种药物导致所有动物死亡的剂量下，组合在注射和吸入模型中分别产生 80%和 40%的存活率。同样，单独使用任何一种药物产生 40%存活率的药物剂量，在注射和吸入模型中分别产生 80%和 100%的存活率。作为吸入模型的一部分，我们开发了一种新的范式，其中动物暴露于氰化氢气体中，肌肉内注射解毒剂，然后再次暴露于氰化氢气体中。这模拟了大量人员在封闭空间中接触氰化物的情况，因为即使在接受解毒剂后，人们仍会继续接触氰化物。
结论
钴胺酰胺和磺酸钠的联合使用为治疗氰化物中毒提供了一种新的方法，具有很大的前景。
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