In this review, the current progress in the research and development of butyrylcholinesterase (BChE) reactivators is summarised and the advantages or disadvantages of these reactivators are critically discussed. Organophosphorus compounds such as nerve agents (sarin, tabun, VX) or pesticides (chlorpyrifos, diazinon) cause irreversible inhibition of acetylcholinesterase (AChE) and BChE in the human body. While AChE inhibition can be life threatening due to cholinergic overstimulation and crisis, selective BChE inhibition has presumably no adverse effects. Because BChE is mostly found in plasma, its activity is important for the scavenging of organophosphates before they can reach AChE in the central nervous system. Therefore, this enzyme in combination with its reactivator can be used as a pseudo-catalytic scavenger of organophosphates. Three structural types of BChE reactivators were found, i.e. bisquaternary salts, monoquaternary salts and uncharged compounds. Although the reviewed reactivators have certain limitations, the promising candidates for BChE reactivation were found in each structural group.

• MeSH
• acetylcholinesterasa metabolismus   chemie   MeSH
• butyrylcholinesterasa * metabolismus   chemie   MeSH
• cholinesterasové inhibitory * chemie   farmakologie   chemická syntéza   MeSH
• lidé MeSH
• molekulární struktura MeSH
• organofosforové sloučeniny * chemie   farmakologie   MeSH
• reaktivátory cholinesterázy farmakologie   chemie   chemická syntéza   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

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