Four novel bisquaternary aldoxime cholinesterase reactivators differing in their chemical structure were prepared. Afterwards, their biological activity was evaluated for their ability to reactivate acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibited by paraoxon. Their reactivation activity was compared with standard reactivators--pralidoxime, obidoxime and HI-6--which are clinically used at present. As it resulted, none of the prepared compounds surpassed obidoxime, which is considered to be the most potent compound if used for reactivation of AChE inhibited by paraoxon. In case of BuChE reactivation, two compounds (K053 and K068) achieved similar results as obidoxime.
- MeSH
- acetylcholinesterasa účinky léků metabolismus MeSH
- butyrylcholinesterasa účinky léků metabolismus MeSH
- enzymové reaktivátory farmakologie MeSH
- magnetická rezonanční spektroskopie MeSH
- oximy chemie MeSH
- paraoxon farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Preparation of 1-(4-hydroxy-iminomethylpyridinium)-3-pyridiniumpropane dibromide is described. This compound represents a new acetylcholinesterase (AChE) reactivator, which has no substituents on the second pyridinium ring as found in other commonly used AChE reactivators. The reactivation ability of this reactivator was tested on tabun- and cyclosarin-inhibited AChE. According to the results obtained, the new compound (without substitution and with decreased molecule size) showed increased reactivation potency in case of cyclosarin inhibited AChE. A potent oxime for treatment of tabun and cyclosarin-caused intoxications was thus obtained via slight modification of the reactivator structure (compared to trimedoxime and K027).
- MeSH
- acetylcholinesterasa diagnostické užití MeSH
- financování organizované MeSH
- lidé MeSH
- organofosfáty antagonisté a inhibitory MeSH
- organofosforové sloučeniny antagonisté a inhibitory MeSH
- oximy chemická syntéza MeSH
- pyridinové sloučeniny chemická syntéza MeSH
- reaktivátory cholinesterasy chemická syntéza MeSH
- Check Tag
- lidé MeSH
The potency of newly developed asymmetric bispyridinium oximes (K027, K048) in reactivating tabun-inhibited acetylcholinesterase (AChE) and in eliminating tabun-induced acute toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined the percent of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats and showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime, the most efficacious known reactivators of tabun-inhibited AChE. These were also found to be sufficiently efficacious in the elimination of acute lethal toxic effects in tabun-poisoned rats. The oxime HI-6, relatively efficacious against soman, did not seem to be an adequately effective oxime in reactivation of tabun-inhibited AChE and in counteracting acute lethal effects of tabun. In addition, our results confirm that the efficacy of oximes in reactivating tabun-inhibited AChE in blood, diaphragm, and brain correlates with the potency of oximes in protecting rats poisoned with supralethal doses of tabun.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- aktivace enzymů MeSH
- bránice enzymologie MeSH
- chemické bojové látky otrava MeSH
- financování organizované MeSH
- krysa rodu rattus MeSH
- mozek enzymologie MeSH
- organofosfáty MeSH
- otrava organofosfáty MeSH
- otrava farmakoterapie MeSH
- oximy farmakologie MeSH
- potkani Wistar MeSH
- pyridinové sloučeniny farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
