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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Oxime effects on the rate constants of carbamylation and decarbamylation of acetylcholinesterase for pyridostigmine, physostigmine and insecticidal carbamates.

The effects of the oximes 2-pyridine aldoxime methiodide (PAM), HI-6, HS-6, toxogonin and TMB-4 on the rate of carbamylation of membrane-bound bovine erythrocyte acetylcholinesterase were studied. The second-order rate constant of carbamylation (ki) and the first-order rate constant of decarbamylation (k3) were calculated from the proportion of free acetylcholinesterase at equilibrium and the rate of approach to equilibrium. Twenty insecticidal carbamates plus physostigmine and pyridostigmine were studied. The oximes increased ki for several carbamates, with HI-6 causing an increase in the most number of cases (12) and PAM the least (3). HI-6 was also a potent accelerator of decarbamylation (increase in k3) in all cases, whereas PAM caused a significant decrease in k3 in 15 cases and a nonsignificant decrease in the other 7. Toxogonin and TMB-4 increased k3 or had no significant effect. The results were generally consistent with a proposal in the literature that there is a correlation between increased ki and increased toxicity of the carbamate in the presence of an oxime.[1]

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