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© 1991 Oxford University Press

other

Toxicity of Organophosphate Nerve Agents and Related Phosphonylated Oximes Compared to Their Anticholinesterase Activity in Neuron Cultures

T. W. SAWYER, M. T. WEISS, C. A. BOULET and A. S. HANSEN

Biomedical Defence Section, Defence Research Establishment Suffield Box 4000, Medicine Hat, Alberta

Received October 9, 1990; accepted February 26, 1991

Toxicity of Organophosphate Nerve Agents and Related Phosphonylated Oximes Compared to Their Anticholinesterase Activity in Neuron Cultures. SAWYER, T. W., WEISS, M. T., BOULET, C. A., AND HANSEN, A. S. (1991). Fundam. Appl. Toxicol. 17, 208-214. Oximes, such as prali-doxime and toxogonin, are important therapeutic agents for the treatment of organophosphate (OP) nerve agent poisoning. Oximes can react with these nerve agents to give intermediates, phosphonylated oximes, which may be equally toxic to the parent OP. The sc LD50s of a series of phosphonylated 2-butanone and 2,3-butanedione monoximes were compared to the sc LD50s of their parent OPs (tabun, sarin, and VX) in CD-I mice. In every case the derivatives were significantly less toxic than their parent nerve agents. Times to death, and to signs of poisoning, were inversely proportional to the dose of test compound, and in all mortalities, blood serum acetylcholinesterase (AChE) was severely inhibited. The relative potencies of these compounds, as well as soman, cyclohexyl methylphosphonofluoridate, and diisopropyl fluorophosphate, as inhibitors of AChE in primary cultures of mouse embryo neurons, correlated with their in vivo toxicities. The results indicate that mouse embryo neuron cultures may be a useful model with which to study this class of compounds.


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