HI-6 therapy of soman and tabun poisoning in primates and rodents.
The bis-pyridinium oxime HI-6, in conjunction with atropine, was found to offer significant protection against multiple LD50 challenges with the organophosphorus compounds soman and tabun. In adult rhesus macaques, the therapeutic administration of HI-6 with atropine and diazepam protected three of four animals from the lethal effects of 5 x LD50 of soman and three of three animals from 5 x LD50 of tabun. However, when toxogonin was substituted for HI-6 in the therapeutic mixture, all three animals poisoned with 5 x LD50 of soman died. In rats, the 24 h protective ratios against tabun and soman with HI-6 were 2 and 3.5, respectively, whereas in guinea pigs these values were between 4 and 6 for both agents. No evidence was obtained for acetylcholinesterase (AChE) reactivation by HI-6 in tissue from tabun-poisoned rodents or following soman or tabun in primate plasma. The results underscore the significant therapeutic benefit of HI-6 in primates, a species specific efficacy against tabun, and argue for some mechanism of action of HI-6 at least partly unrelated to AChE reactivation.
Hamilton
M G
MG
Defence Research Establishment Suffield, Ralston, Alberta, Canada.
Lundy
P M
PM
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008253:Macaca mulatta; D008297:Male; D062025:Organophosphate Poisoning; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012132:Respiratory Muscles / Q000201:enzymology / Q000378:metabolism; D012999:Soman / Q000506:poisoning*
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D012999:Soman; D000110:Acetylcholinesterase; C022870:asoxime chloride; C009374:tabun