Comparison of acetylcholinesterase, pyridostigmine, and HI-6 as antidotes against organophosphorus compounds
Conventional medical treatment against the toxicity of organophosphorus (OP) compounds consists of a regimen of anticholinergic drugs to counteract the accumulation of acetylcholine and oximes to reactivate OP-inhibited acetylcholinesterase (AChE) (Taylor, 1985). Reactivation ofOP-inhibited AChE by oximes can generate enough active AChE in the peripheral nervous system, especially in the diaphragm, to restore normal cholinergic neurotransmission after exposure to many OP compounds. However, some OP compounds, such as soman (pinacolylmdhylphos phonofluofldate), inhibit AChE and rapidly age into a form that cannot be reactivated by oximes (De Jong and Wolring, 1984), thereby reducing the ability of oximes to provide protection (Maxwell and Brecht, 1991). The inability of oximes to provide adequate protection against the toxicity of rapidly aging OP compounds stimulated the development of carbamate pretreatment in which carbamylation of AChE effectively protects it against inhibition by OP compounds (Leadbeater et al., 1985). Spontaneous decarbamylation of AChE after the OP compound has been detoxified then generates enough active AChE to allow normal cholinergic neurotransmission. Behavioral side effects from carbamate pretreatment in the absence of exposure to OP compounds have been avoided by the use of cationic pretreatment carbamates, such as pyridostigmine, which do not enter the central nervous system.
- Research Organization:
- Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (United States)
- OSTI ID:
- 236854
- Report Number(s):
- AD-A--302514/5/XAB; USAMRICD-P--94-031
- Country of Publication:
- United States
- Language:
- English
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