ISSN 1214-0287 (on-line), ISSN 1214-021X (printed)
J Appl Biomed
Volume 8 (2010), No 2, p 87-92
DOI 10.2478/v10136-009-0008-6

The effect of trimedoxime on acetylcholinesterase and on the cholinergic system of the rat bladder

Ondrej Soukup, Ondrej Holas, Jiri Binder, Kumar Killy, Gunnar Tobin, Daniel Jun, Josef Fusek, Kamil Kuca

Address: Kamil Kuca, Centre of Advanced Studies, Department of Toxicology, Faculty of Military Health Science, University of Defense, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic
kucakam@pmfhk.cz

Received 20th August 2009.
Published online 13th January 2010.

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SUMMARY
Trimedoxime is a bisquaternary oxime that is widely used in the treatment of organophosphorous poisoning caused by tabun and paraoxon. We tested its affinity to acetylcholinesterase (AChE), its mechanism of interaction and effect on the cholinergic system of the rat bladder. The half maximal inhibitory concentration (IC50) of trimedoxime to recombinant AChE was found to be 82.0 mM ± 30.1 mM. This represents a weak inhibition. Its interaction with AChE seems to be very similar to obidoxime - one aromatic nucleus interacts with the peripheral anionic site and the other with the residues TYR337 and TYR341 inside the cavity. Also the oxime moiety is moving towards the catalytic triade ready for the reactivation of the inhibited AChE. In the organ bath experiment no significant effect of trimedoxime was observed on the contraction of the detrusor caused by the muscarinic agonist metacholine.

KEY WORDS
acetylcholinesterase; trimedoxime; antidote; muscarinic receptors; reactivation


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CITED

Zdarova Karasova Jana, Hnidkova D, Pohanka M, Musilek K, Chilcott RP, Kuca K. Pharmacokinetics of acetylcholinesterase reactivator K203 and consequent evaluation of low molecular weight antioxidants/markers of oxidative stress. J Appl Biomed. 10: 71-78, 2012.

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