The combination of cobinamide and sulfanegen is highly effective in mouse models of cyanide poisoning.
The combination of cobinamide and sulfanegen is highly effective in mouse models of cyanide poisoning.
复制标题
DOI：
10.3109/15563650.2011.584879
复制
发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Boss GR
中科院分区：
文献类型：
--
作者：
Chan A;Crankshaw DL;Monteil A;Patterson SE;Nagasawa HT;Briggs JE;Kozocas JA;Mahon SB;Brenner M;Pilz RB;Bigby TD;Boss GR
氰化物中毒是烟雾吸入受害者死亡的主要原因，各种行业都发生了意外接触氰化物的事件。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。目前氰化物中毒的治疗方法必须通过静脉给药，限制了它们在治疗大规模伤亡方面的使用。我们正在开发两种新的氰化物解毒剂--维生素B12类似物椰子酰胺和3-硫代丙酮酸前体药物磺胺。这两种药物都可以通过肌肉注射给药，因此可以用来快速治疗大量患者。我们现在问的是，当这两种药物联合使用时，是否会产生增强效应。我们使用了一种非致命性和两种不同致命性的氰化物中毒小鼠模型。非致命性模型通过定量评估小鼠天生的翻正反射时间来评估神经恢复。这两种致命模式是氰化物注射和氰化物吸入模式。我们发现，在非致死和致死模型中，这两种药物至少是相加的：在单独使用其中一种药物导致所有动物死亡的剂量下，联合使用分别在注射和吸入模型中产生80%和40%的存活率。同样，在注射和吸入模型中，单独使用任何一种药物产生40%存活率的药物剂量分别产生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，即动物暴露在氰化物气体中，肌肉注射解毒剂，然后再次暴露在氰化物气体中。这模拟了大量人在封闭的空间中接触氰化物，因为即使在接受解毒剂后，人们仍会暴露在氰化物中。可比酰胺和磺胺的结合显示出作为治疗氰化物中毒的一种新方法的巨大前景。
Cyanide poisoning is a major contributor to death in smoke inhalation victims 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. We are developing two new cyanide antidotes—cobinamide, a vitamin B12 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. 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. 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 inhalatiion models, respectively. As part of the inhalation model, we developed a new paradigm in which animals are exposed to cyanide gas, injected intramuscularly with 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. The combination of cobinamide and sulfanegen shows great promise as a new approach to treating cyanide poisoning.
登录
查看更多内容
影响因子：
158.5
作者：
BAUD, FJ;BARRIOT, P;BISMUTH, C
通讯作者：
BISMUTH, C
影响因子：
3.3
作者：
Borron, Stephen W.;Stonerook, Michael;Reid, Frances
通讯作者：
Reid, Frances
影响因子：
2.7
作者：
Ernesto, M;Cardoso, AP;Bradbury, JH
通讯作者：
Bradbury, JH
影响因子：
7.3
作者：
Nagasawa, Herbert T.;Goon, David J. W.;Patterson, Steven E.
通讯作者：
Patterson, Steven E.
DOI：
10.1016/s1096-4959(03)00003-4
发表时间：
2003-03-01
影响因子：
2.2
作者：
Nazifi, S;Aminlari, M;Alaibakhsh, MA
通讯作者：
Alaibakhsh, MA