Reactivation of Acetylcholinesterase Activity and Its Therapeutic Benefits in Nerve Agent Intoxication

Organophosphorus chemical warfare nerve agents are potent inhibitors of the enzyme acetylcholinesterase (AChE). Inhibition of AChE at nerve terminals in peripheral tissues and the central nervous system (CNS) results in acetylcholine (ACh) overload and, depending on the extent of enzyme inhibition,...

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Bibliographic Details
Main Authors: Shih, Tsung-Ming, Maxwell, Donald M, Koplovitz, Irwin, Kan, Robert K, McDonough, John H
Format: Report
Language:English
Subjects:
2-PAM(PYRIDINE-2-ALDOXIME METHYLCHLORIDE)
ACETYLCHOLINE
ACETYLCHOLINESTERASE
ACH(ACETYLCHOLINE)
ACHE(ACETYLCHOLINESTERASE)
ATROPINE
Biochemistry
CENTRAL NERVOUS SYSTEM
CHE(CHOLINESTERASE)
CHEMICAL WARFARE AGENTS
Chemical, Biological and Radiological Warfare
CHOLINESTERASE INHIBITORS
CNS(CENTRAL NERVOUS SYSTEM)
DAM(DIACETYLMONOOXIMES)
ELECTROENCEPHALOGRAPHY
EXPOSURE(PHYSIOLOGY)
G AGENTS
GRAPHS
GUINEA PIGS
IM(INTRAMUSCULAR)
IP(INTRAPERITONEAL)
MEDIAN LETHAL DOSE
MEDICAL COUNTERMEASURES
Medicine and Medical Research
OP(ORGANOPHOSPHORUS COMPOUNDS)
Organic Chemistry
ORGANIC PHOSPHORUS COMPOUNDS
OXIMES
Pharmacology
PR(PROTECTIVE RATIO)
RBC(RED BLOOD CELLS)
REACTIVATION
SC(SUBCUTANEOUS)
SULFATES
TABLES(DATA)
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Summary:Organophosphorus chemical warfare nerve agents are potent inhibitors of the enzyme acetylcholinesterase (AChE). Inhibition of AChE at nerve terminals in peripheral tissues and the central nervous system (CNS) results in acetylcholine (ACh) overload and, depending on the extent of enzyme inhibition, cholinergic crisis. Current treatment strategies for nerve agent intoxication consist of using an oxime such as pyridine-2-aldoxime methylchloride (2-PAM) to reactivate the inhibited AChE and the anticholinergic drug atropine sulfate to antagonize the effects of excess ACh at muscarinic cholinergic receptors. Published in the Neurochemical Consequences of Organophosphate Poisoning in the CNS, p111-133, 2010. The original document contains color images.