Comparison of 2-PAM and pro-2-PAM containing treatment regimens as antagonists of nerve agent-induced lethality and incapacitation. Final report, June 1981-December 1985

Technical Report · Mon Sep 01 00:00:00 EDT 1986

OSTI ID:6909591

Talbot, B G; Harris, L W; Lennox, W J; Anderson, D A; Green, M D

In vivo, (2-Puridine Aldoxine Methioidide) reactivates phosphonylated acetylcholinesterase AChE peripherally, but is effective in restoring AChE centrally because the quaternary nitrogen atom of 2-PAM prevents penetration of the brain. The problem was solved by the synthesis of the 1,6-dihyropyridine derivative of 2-PAM, pro-2-PAM (PP). Functional brain AChE is related to return to control performance on an accelerating rotarod (ARR) in animals intoxicated with soman. There should be a difference in the time to recovery of control ARR performance between PP- and 2-PAM-treated, sarin-intoxicated animals. In the present work, an ARR decrement free dosage (DFD) of each of these oximes (30 mg/kg, im) in combination with DFD of atropine (A) and mecamylamine (M) (0.79 mg/kg each, im) was used as pretreatment against sarin-induced deficit. The same antidotes were given pre-and post- intoxication (as pretreatment and therapy) to anatagonize sarin-induced lethality; the PP containing antidote provided significantly greater protection than that by the 2-PAM antidote which in turn provided significant protection over control. Neither antidote when given as pretreatment and therapy provided protection above control against soman-induced physical incapacitation, but they were equally effective in antagonizing VX-induced physical incapacitation. The reversal of sarin-induced physical debilitation reflects the central actions of PP and supports the notion that functional brain AChE activity is essential for rapid recovery from the debilitating effeclts on nerve agents.

• Research Organization: Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (USA)
• OSTI ID: 6909591
• Report Number(s): AD-A-173018/3/XAB; USAMRICD-SP-86-012
• Country of Publication: United States
• Language: English

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37 INORGANIC
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BRAIN
CHOLINESTERASE
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OXIMES
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ENZYMES
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ORGANIC NITROGEN COMPOUNDS
ORGANS
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400201* - Chemical & Physicochemical Properties