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

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 x LD50 dose of soman, sarin and GF and 2 x 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 greater than 150, 5.88, 100 and 71 mg/kg against poisoning by soman, sarin, GF and tabun, respectively. HLö-7 produced significant (p less than 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.
AuthorsJ G Clement, A S Hansen, C A Boulet
JournalArchives of toxicology (Arch Toxicol) Vol. 66 Issue 3 Pg. 216-9 ( 1992) ISSN: 0340-5761 [Print] Germany
PMID1497487 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Antidotes
  • Cholinesterase Inhibitors
  • Cholinesterase Reactivators
  • Imidazoles
  • Neuromuscular Blocking Agents
  • Organophosphates
  • Oximes
  • Pyridines
  • Pyridinium Compounds
  • HLo 7
  • pyrimidoxime
  • Soman
  • Sarin
  • asoxime chloride
  • tabun
Topics
  • Animals
  • Antidotes (pharmacology)
  • Cholinesterase Inhibitors (poisoning)
  • Cholinesterase Reactivators (pharmacology)
  • Imidazoles (pharmacology, toxicity)
  • Lethal Dose 50
  • Male
  • Mice
  • Neuromuscular Blocking Agents (poisoning)
  • Organophosphate Poisoning
  • Organophosphates
  • Oximes
  • Pyridines (pharmacology, toxicity)
  • Pyridinium Compounds (pharmacology, toxicity)
  • Sarin (poisoning)
  • Soman (poisoning)

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