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首页> 美国政府科技报告 >Effects of Methemoglobin Formers on Spontaneous Locomotor Activity and Methemoglobin Levels in Mice
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Effects of Methemoglobin Formers on Spontaneous Locomotor Activity and Methemoglobin Levels in Mice

机译：高铁血红蛋白形成因子对小鼠自发运动能力和高铁血红蛋白水平的影响

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摘要

Cyanide (CN) remains a viable threat as a chemical warfare agent. Methemoglobin (MHb) formation is one strategy used to counter CN toxicity. It has been suggested that blood levels of 5-12% MHb will protect a human against a 2X MLD (median lethal dose) of CN. Available MHb formers present certain drawbacks and limitations. To identify improved MHb formers, we characterized the locomotor activity effects and MHb formation capacity of three MHb formers with established efficacy against CN (p-aminopropiophenone PAPP, p- aminoheptanoylphenone PAHP and p-aminooctanoylphenone PAOP) as a function of time, dose (9.4-125.0 mg/kg) and route of administration (IM versus IP). Mice received a single injection of a test compound or its solvent, and were either placed in an automated activity monitoring chamber for 1 hr or monitored for MHb levels for 3 hr. Sodium nitrite (100 mg/kg) served as the positive control. Dose-related MHb formation was observed for each compound. A typical time- dependent decline in activity was exhibited in negative control groups and in drug-treated groups that exhibited greater than 20% MHb. A route of administration effect was also observed with PAHP and PAOP. These locomotor activity data, combined with other findings, support the idea that compounds producing low MHb levels can be effective against CN without debilitating side effects.

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