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Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice

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Abstract

The toxicity and efficacy of two oximes, HLö-7 and pyrimidoxime, were evaluated in mice and compared to those obtained with HI-6. HLö-7 and pyrimidoxime produced 24 h LD50 values of 356 and 291 mg/kg (i.p.), respectively. In combination with atropine (17.4 mg/kg, i.p.), HLö-7 was a very efficient therapy against poisoning by 3×LD50 dose of soman, sarin and GF and 2×LD50 dose of tabun with ED50 values of 12.4, 0.31, 0.32 and 25.2 mg/kg, respectively. In contrast, pyrimidoxime was a relatively poor therapy which resulted in ED50 values of >150, 5.88, 100 and 71 mg/kg against poisoning by soman, sarin, GF and tabun, respectively. HLö-7 produced significant (p <0.05) reactivation of phosphorylated acetylcholinesterase, in vivo, resulting in 47, 38, 27 and 10% reactivation of sarin, GF, soman and tabun inhibited mouse diaphragm acetylcholinesterase, respectively. HLö-7 also antagonized sarin-induced hypothermia in mice suggesting that it reactivated central acetylcholinesterase. The potential of HLö-7 as a replacement oxime for the treatment of nerve agent poisoning is discussed.

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Authors and Affiliations

  1. Biomedical Defence, Defence Research Establishment Suffield, Ralston, Alta., Canada

    John G. Clement

  2. Chemical/Biological Defence Sections, Defence Research Establishment Suffield, Ralston, Alta., Canada

    Arnold S. Hansen & Camille A. Boulet

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  1. John G. Clement
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  2. Arnold S. Hansen
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  3. Camille A. Boulet
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Clement, J.G., Hansen, A.S. & Boulet, C.A. Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice. Arch Toxicol 66, 216–219 (1992). https://doi.org/10.1007/BF01974018

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  • DOI: https://doi.org/10.1007/BF01974018

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