Organophosphate intoxication: Molecular consequences, mechanisms and solutions

Brian C. Geyer, Tama Evron, Hermona Soreq, Tsafrir Leket-Mor

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

The essential role of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ) predicts severe consequences following loss of function by its irreversible inhibition. The vital role of the acetylcholine-hydrolyzing enzyme AChE in terminating cholinergic neurotransmission has been recognized for almost as many years. Anticholinesterases can be commonly encountered as industrial pesticides, weapons of war, Alzheimer's medications as well as the natural toxins of many organisms including fungi, plants, and animals. Exposure to clinically relevant doses of anticholinesterases results in immediate and multisystem physiological disturbances that underscore the broad anatomical distribution of the mammalian cholinergic system. The body adapts to the insult and attempts to compensate for the cholinergic dysregulation by inhibitor-enzyme interactions, NMJ remodeling, and changes in circulating cytokine profiles. In addition the loss of synaptic cholinergic regulation by AChE inhibition has immediate negative consequences for mammalian physiology. The severe multisystem clinical presentation of anti-ChE intoxication demonstrates the essential and ubiquitous nature of the mammalian cholinergic system. Current medical intervention in the case of acute exposure to anticholinesterase agents includes use of the muscarinic receptor antagonist atropine to block overstimulation, and oximes to reactivate the OP-modified AChE. The reversible carbamate inhibitor, pyridostigmine bromide, is also used for prophylaxis.

Original languageEnglish (US)
Title of host publicationHandbook of Toxicology of Chemical Warfare Agents
PublisherElsevier Inc.
Pages691-717
Number of pages27
ISBN (Print)9780123744845
DOIs
StatePublished - Dec 1 2009

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Geyer, B. C., Evron, T., Soreq, H., & Leket-Mor, T. (2009). Organophosphate intoxication: Molecular consequences, mechanisms and solutions. In Handbook of Toxicology of Chemical Warfare Agents (pp. 691-717). Elsevier Inc.. https://doi.org/10.1016/B978-012374484-5.00046-8