Antidotal efficacy of bisquaternary oximes against soman and tabun poisoning in various species
The introduction of Hagedorn oximes, e.g. HI-6 and HLo-7, was an important milestone in the development of antidotal treatment against soman poisoning. We have developed a series of 'cholinergic receptor-directed' AB-oximes which combine in their molecular structure both AChE reactivation potency and anti-cholinergic properties. Marked antidotal efficacy against soman and tabun poisoning was obtained for AB-8, AB-13, toxogonin, HLo-7 and HI-6 in conjunction with atropine and benactyzine in pyridostigmine (PYR) pretreated mice and guinea pigs. In the absence of PYR, all oximes except for HI-6 in mice or HI-6 and HLo-7 in guinea pigs provided poor protection (PR=1-2) against soman. In tabun poisoning, AB-13, toxogonin and HLO-7 conferred high PR values: 8.6, 21.3 and 21.7, respectively, even without PYR pretreatment. These data are consistent with reactivation potency of these oximes (kr = 12.5, 157 and 18.7 m(1) min(1), respectively) for tabun-inhibited FBS-AChE. Elimination of benactyzine significantly decreased the PR values obtained against soman in guinea pigs.
- Research Organization:
- Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (United States)
- OSTI ID:
- 7113567
- Report Number(s):
- AD-P-008809/6/XAB
- Country of Publication:
- United States
- Language:
- English
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