Oxons anticholinesterase activity

In the case of activation reactions, such as the activation of the insecticide azin-phosmethyl to its potent anticholinesterase oxon derivative, a decrease in toxicity is apparent when rats are pretreated with the P450 inhibitor SKF-525A. 

One non-anticholinesterase effect of OPs has been discussed in section 10.3.1.3, namely OPIDP. The degree to which non-acetylcholinesterase inhibition effects contribute to acute OP toxicity continues to be a matter of interest and has been reviewed. Thus, Chambers " noted a poor correlation between rat oral LD50 values of various phosphorothionate insecticides and inhibition potency of corresponding oxons for brain acetylcholinesterase. However, there are a number of possible explanations for this, other than differences in target molecule notably, differences in site and magnitude of desulfuration of the thionate to the active oxon may be important. Studies by Duysen and colleagues with acetylcholinesterase knockout mice suggested that non-acetylcholinesterase inhibitory effects must contribute to the acute toxicity of VX. Maxwell et... 

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