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Accession Number ADA583112
Title Tertiary Oximes on Brain Acetylcholinesterase and Central Excitatory Effects of Nerve Agents.
Publication Date 2012
Media Count 18p
Personal Author K. A. Jeffrey M. H. John S. Tsung-Ming
Abstract Abstract. Organophosphorus nerve agents irreversibly inhibit the enzyme acetylcholinesterase (AChE), which leads to an excess of the cholinergic neurotransmitter acetylcholine in the synapses causing numerous toxic effects, including prolonged seizures and subsequent neuropathology. Current nerve agent therapies include pralidoxime (2-PAM) to reactivate inhibited AChE. The quaternary structure of this oxime does not allow it to cross the blood brain barrier (BBB) to reactivate brain AChE and to mitigate CNS toxicity. This study examined whether monoisonitrosoacetone (MINA) and N,N-diethyl-3-(2- (hydroxyimino)acetoxy) propan-1-aminium chloride (DHAP), two tertiary oximes that can penetrate the BBB, could prevent or reverse the central toxic effects of three nerve agents, sarin (GB), cyclosarin (GF), or VX, in guinea pigs. The first experiment tested whether MINA and DHAP could reactivate brain and peripheral tissue AChE inhibited by these nerve agents. Animals were challenged with a 1.0 x LD50 subcutaneous dose of a nerve agent and followed 15 min by one of 5 test doses of the oxime.
Keywords Acetylcholine
Acetylcholinesterase
Blood brain barrier
Brain
Central nervous system
Chemical agents
Cholinergic nerves
Convulsive disorders
Dosage
Enzymes
Gb agent
Nerve agents
Neurotransmitters
Organic phosphorus compounds
Oximes
Pain
Penetration
Subcutaneous tissue
Synapse
Toxicity


 
Source Agency Non Paid ADAS
NTIS Subject Category 74D - Chemical, Biological, & Radiological Warfare
57E - Clinical Medicine
Corporate Author Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD.
Document Type Journal article
Title Note Journal article.
NTIS Issue Number 1401
Contract Number N/A

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