Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice.
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.
Clement
J G
JG
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alta., Canada.
Hansen
A S
AS
Boulet
C A
CA
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009466:Neuromuscular Blocking Agents / Q000506:poisoning*; D062025:Organophosphate Poisoning; D010755:Organophosphates; D010091:Oximes; D011725:Pyridines / Q000494:pharmacology* / Q000633:toxicity; D011726:Pyridinium Compounds / Q000494:pharmacology* / Q000633:toxicity; D012524:Sarin / Q000506:poisoning; D012999:Soman / Q000506:poisoning
D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D007093:Imidazoles; D009466:Neuromuscular Blocking Agents; D010755:Organophosphates; D010091:Oximes; D011725:Pyridines; D011726:Pyridinium Compounds; C058577:HLo 7; C066214:pyrimidoxime; D012999:Soman; D012524:Sarin; C022870:asoxime chloride; C009374:tabun