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.
- Klíčová slova
- acetylcholinesterase, trimedoxime, antidote, muscaricnic receptors, reactivation,
- MeSH
- acetylcholinesterasa farmakokinetika farmakologie účinky léků MeSH
- antidota farmakologie terapeutické užití MeSH
- cholinergní antagonisté farmakokinetika farmakologie terapeutické užití MeSH
- cholinergní látky farmakologie imunologie izolace a purifikace MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- močový měchýř MeSH
- organofosforové sloučeniny farmakokinetika farmakologie toxicita MeSH
- pesticidy farmakokinetika farmakologie toxicita MeSH
- potkani Sprague-Dawley MeSH
- reaktivátory cholinesterázy farmakokinetika farmakologie terapeutické užití MeSH
- receptory muskarinové účinky léků MeSH
- synergismus léků MeSH
- trimedoxim farmakokinetika farmakologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
