Investigation of kinetic interactions between approved oximes and human acetylcholinesterase inhibited by pesticide carbamates.

Timo Wille, Lisa Kaltenbach, Horst Thiermann, Franz Worek

Index: Chem. Biol. Interact. 206(3) , 569-72, (2013)

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Abstract

Carbamates are widely used for pest control and act primarily by inhibition of insect and mammalian acetylcholinesterase (AChE). Accidental or intentional uptake of carbamates may result in typical signs and symptoms of cholinergic overstimulation which cannot be discriminated from those of organophosphorus pesticide poisoning. There is an ongoing debate whether standard treatment with atropine and oximes should be recommended for human carbamate poisoning as well, since in vitro and in vivo animal data indicate a deleterious effect of oximes when used in combination with the N-methyl carbamate carbaryl. Therefore, we performed an in vitro kinetic study to investigate the effect of clinically used oximes on carbamoylation and decarbamoylation of human AChE. It became evident that pralidoxime and obidoxime in therapeutic concentrations aggravate the inhibition of AChE by carbaryl and propoxur, with obidoxime being substantially more potent compared to 2-PAM. However, obidoxime had no impact on the decarbamoylation kinetics. Hence, the administration of 2-PAM and especially of obidoxime to severely propoxur and carbaryl poisoned humans cannot be recommended. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.