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

The potency of newly developed bispyridinium compounds (K117, K127) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oxime (obidoxime) using functional observational battery. The neuroprotective effects of atropine alone and atropine combined with one of three bispyridinium oximes (K117, K127, obidoxime) on rats poisoned with tabun at a sublethal dose (180 microg/kg i.m.; 80% of LD(50) value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 24 h following tabun challenge while one tabun-poisoned rats died within 24 h after tabun poisoning when the rats were treated with atropine alone. Newly developed oxime K127 combined with atropine was the most effective in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Nevertheless, the differences of neuroprotective efficacy between K127 and obidoxime are not sufficient to replace obidoxime by K127 for the treatment of acute tabun poisonings.

• MeSH
• chemické bojové látky otrava   MeSH
• cholinesterasové inhibitory otrava   MeSH
• krysa rodu Rattus MeSH
• neuroprotektivní látky farmakologie   MeSH
• organofosfáty MeSH
• otrava organofosfáty * MeSH
• oximy farmakologie   MeSH
• pohybová aktivita účinky léků   MeSH
• potkani Wistar MeSH
• pyridinové sloučeniny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• chemické bojové látky MeSH
• cholinesterasové inhibitory MeSH
• K117 compound MeSH Prohlížeč
• K127 compound MeSH Prohlížeč
• neuroprotektivní látky MeSH
• organofosfáty MeSH
• oximy MeSH
• pyridinové sloučeniny MeSH
• tabun MeSH Prohlížeč