This article describes acetylcholinesterase (AChE), an enzyme involved in parasympathetic neurotransmission, its activity, and how its inhibition can be pharmacologically useful for treating dementia, caused by Alzheimer's disease, or as a warfare method due to the action of nerve agents. The chemical concepts related to the irreversible inhibition of AChE, its reactivation, and aging are discussed, along with a relationship to the current international legislation on chemical weapons.

• Klíčová slova
• Alzheimer’s disease, Chemical Weapons Convention, acetylcholinesterase, nerve agents,
• MeSH
• acetylcholinesterasa * metabolismus   MeSH
• Alzheimerova nemoc * farmakoterapie   enzymologie   MeSH
• chemická válka zákonodárství a právo   MeSH
• cholinesterasové inhibitory terapeutické užití   MeSH
• GPI-vázané proteiny antagonisté a inhibitory   metabolismus   MeSH
• lidé MeSH
• nervová bojová látka * MeSH
• stárnutí metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• acetylcholinesterasa * MeSH
• ACHE protein, human MeSH Prohlížeč
• cholinesterasové inhibitory MeSH
• GPI-vázané proteiny MeSH
• nervová bojová látka * MeSH

The ability of two newly developed oximes (K305, K307) to protect tabun-poisoned rats from tabun-induced inhibition of brain acetylcholinesterase, acute neurotoxic signs and symptoms and brain damage was compared with that of the oxime K203 and trimedoxime. The reactivating and neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose were evaluated. The reactivating efficacy of a newly developed oxime K305 is lower compared to the reactivating efficacy of the oxime K203 and trimedoxime while the ability of the oxime K307 to reactivate tabun-inhibited acetylcholinesterase (AChE) in the brain roughly corresponds to the reactivating efficacy of the oxime K203 and it is slightly lower compared to trimedoxime. In addition, only one newly developed oxime (K307) combined with atropine was able to markedly decrease tabun-induced neurotoxicity although it did not eliminate all tabun-induced acute neurotoxic signs and symptoms. These results correspond to the histopathological evaluation of tabun-induced brain damage. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes (especially trimedoxime) in the treatment of acute tabun poisonings.

• Klíčová slova
• acetylcholinesterase, functional observational battery, histopathology, neurotoxicity, oximes, rats, tabun,
• MeSH
• acetylcholinesterasa metabolismus   MeSH
• atropin terapeutické užití   MeSH
• chemické bojové látky otrava   MeSH
• lidé MeSH
• mozek účinky léků   enzymologie   MeSH
• neuroprotektivní látky terapeutické užití   MeSH
• neurotoxické syndromy farmakoterapie   MeSH
• organofosfáty toxicita   MeSH
• otrava organofosfáty farmakoterapie   MeSH
• oximy terapeutické užití   MeSH
• potkani Wistar MeSH
• pyridinové sloučeniny terapeutické užití   MeSH
• reaktivátory cholinesterázy terapeutické užití   MeSH
• trimedoxim terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• atropin MeSH
• chemické bojové látky MeSH
• neuroprotektivní látky MeSH
• organofosfáty MeSH
• oximy MeSH
• pyridinové sloučeniny MeSH
• reaktivátory cholinesterázy MeSH
• tabun MeSH Prohlížeč
• trimedoxim MeSH

Seven new oxime-based acetylcholinesterase reactivators were compared with three currently available ones (obidoxime, trimedoxime, HI-6) for their ability to lessen cholinesterase inhibition in blood and brain of cyclosarin-treated rats. Oximes were given at doses of 5% their LD(50) along with 21 mg/kg atropine five min before the LD(50) of cyclosarin (120 ug/kg) was administered. Blood and brain samples were collected 30 minutes later. The greatest difference between acetylcholinesterase inhibition in blood of cyclosarin-treated rats was found after administration of HI-6 (40%), compared to 22% for trimedoxime and 6% for obidoxime. Only two of the seven newly synthesized oximes had any effect (K203 at 7%, K156 at 5%). Effective oximes against cyclosarin-inhibited plasma butyrylcholinesterase were HI-6 (42%), trimedoxime (11%), and K156 (4%). The oximes were less effective in brain than in blood, with reactivation values for HI-6 30% against acetylcholinesterase and 10% against butyrylcholinesterase. Values for newly synthesized oximes were less than 10% for K206, K269 and K203.

• Klíčová slova
• acetylcholinesterase, butyrylcholinesterase, cyclosarin, oximes, reactivators,
• MeSH
• acetylcholinesterasa krev   metabolismus   MeSH
• atropin farmakologie   MeSH
• krysa rodu Rattus MeSH
• mozek účinky léků   enzymologie   MeSH
• organofosforové sloučeniny toxicita   MeSH
• oximy chemie   farmakologie   MeSH
• potkani Wistar MeSH
• reaktivátory cholinesterázy chemie   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• atropin MeSH
• cyclohexyl methylphosphonofluoridate MeSH Prohlížeč
• organofosforové sloučeniny MeSH
• oximy MeSH
• reaktivátory cholinesterázy MeSH