Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) belongs to the group of highly toxic organophosphorus compounds that may be used as chemical warfare agents for military as well as terrorist purposes. Tabun differs from other highly toxic organophosphates by the fact that commonly used antidotes are not able adequately to prevent tabun-induced acute toxic effects. The neuroprotective effects of four bispyridinium oximes (K075, trimedoxime, HI-6, obidoxime) in combination with atropine on rats poisoned with tabun at a sublethal dose (150 microg/kg i.m.; 80% of LD50 value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h and 7 d following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 7 d following challenge. Trimedoxime combined with atropine was the most effective antidote in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Due to its neuroprotective effects, trimedoxime may be considered to be more suitable oxime for the antidotal treatment of acute tabun exposure than currently used oximes (obidoxime, HI-6) and the newly synthesized oxime K075.

• MeSH
• antagonisté muskarinových receptorů farmakologie   MeSH
• atropin farmakologie   MeSH
• chemické bojové látky otrava   MeSH
• cholinesterasové inhibitory otrava   MeSH
• kombinovaná farmakoterapie MeSH
• krysa rodu Rattus MeSH
• neuroprotektivní látky farmakologie   MeSH
• neurotoxické syndromy farmakoterapie   MeSH
• organofosfáty MeSH
• otrava organofosfáty * MeSH
• oximy farmakologie   MeSH
• potkani Wistar MeSH
• reaktivátory cholinesterázy farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté muskarinových receptorů MeSH
• atropin MeSH
• chemické bojové látky MeSH
• cholinesterasové inhibitory MeSH
• neuroprotektivní látky MeSH
• organofosfáty MeSH
• oximy MeSH
• reaktivátory cholinesterázy MeSH
• tabun MeSH Prohlížeč

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 ability of two newly developed bispyridinium oximes (K920, K923) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the oxime K203 and trimedoxime using a functional observational battery (FOB). The neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose (130 μg/kg i.m.; 80% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by FOB at 2 h after tabun administration. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment while one non-treated tabun-poisoned rat died within 2 h. Both newly developed oximes (K920, K923) combined with atropine were able to markedly decrease tabun-induced neurotoxicity in the case of sublethal poisoning although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to decrease tabun-induced acute neurotoxicity did not prevail the neuroprotective efficacy of trimedoxime and the oxime K203. Therefore, the newly developed oximes are not suitable for the replacement of currently available oximes (especially trimedoxime) in the treatment of acute tabun poisonings.

• Klíčová slova
• K920, K923, Tabun, functional observational battery, neurotoxicity, rats,
• MeSH
• molekulární struktura MeSH
• neuroprotektivní látky chemie   terapeutické užití   MeSH
• neurotoxické syndromy etiologie   prevence a kontrola   MeSH
• organofosfáty toxicita   MeSH
• oximy chemie   terapeutické užití   MeSH
• potkani Wistar MeSH
• pyridinové sloučeniny chemie   terapeutické užití   MeSH
• reaktivátory cholinesterázy chemie   terapeutické užití   MeSH
• trimedoxim chemie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• 1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene MeSH Prohlížeč
• K920 compound MeSH Prohlížeč
• K923 compound MeSH Prohlížeč
• neuroprotektivní látky MeSH
• organofosfáty MeSH
• oximy MeSH
• pyridinové sloučeniny MeSH
• reaktivátory cholinesterázy MeSH
• tabun MeSH Prohlížeč
• trimedoxim MeSH

AIM: The comparison of neuroprotective and central reactivating effects of the oxime K870 in combination with atropine with the efficacy of standard antidotal treatment in tabun-poisoned rats. METHODS: The neuroprotective effects of antidotal treatment were determined in rats poisoned with tabun at a sublethal dose using a functional observational battery 2 h and 24 h after tabun administration, the tabun-induced brain damage was investigated by the histopathological evaluation and central reactivating effects of oximes was evaluated by the determination of acetylcholinesterase activity in the brain using a standard spectrophotometric method. RESULTS: The central reactivating efficacy of a newly developed oxime K870 roughly corresponds to the central reactivating efficacy of pralidoxime while the ability of the oxime HI-6 to reactivate tabun-inhibited acetylcholinesterase in the brain was negligible. The ability of the oxime K870 to decrease tabun-induced acute neurotoxicity was slightly higher than that of pralidoxime and similar to the oxime HI-6. These results roughly correspond to the histopathological evaluation of tabun-induced brain damage. CONCLUSION: The newly synthesized oxime K870 is not a suitable replacement for commonly used oximes in the antidotal treatment of acute tabun poisonings because its neuroprotective efficacy is only slightly higher or similar compared to studied currently used oximes.

• Klíčová slova
• acetylcholinesterase, functional observational battery, histopathology, neurotoxicity, oximes, rats, tabun,
• MeSH
• acetylcholinesterasa MeSH
• antidota farmakologie   MeSH
• chemické bojové látky * toxicita   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• jedy * MeSH
• krysa rodu Rattus MeSH
• organofosfáty * MeSH
• oximy * farmakologie   MeSH
• potkani Wistar MeSH
• pralidoximové sloučeniny MeSH
• pyridinové sloučeniny * farmakologie   MeSH
• reaktivátory cholinesterázy * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• antidota MeSH
• asoxime chloride MeSH Prohlížeč
• chemické bojové látky * MeSH
• cholinesterasové inhibitory MeSH
• jedy * MeSH
• organofosfáty * MeSH
• oximy * MeSH
• pralidoxime MeSH Prohlížeč
• pralidoximové sloučeniny MeSH
• pyridinové sloučeniny * MeSH
• reaktivátory cholinesterázy * MeSH
• tabun MeSH Prohlížeč

AIM: The ability of two newly developed oximes (K727, K733) to reduce tabun-induced acute neurotoxic signs and symptoms was evaluated and compared with currently available trimedoxime in rats. METHODS: The neuroprotective effects of the oximes studied combined with atropine on Wistar rats poisoned with tabun at a lethal dose (380 µg/kg i.m.; 90% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by the functional observational battery consisting of 38 measurements of sensory, motor and autonomic nervous functions at 2 hours following tabun challenge. RESULTS: All tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment. Both newly developed oximes (K727, K733) combined with atropine were able to decrease tabun-induced neurotoxicity in the case of lethal poisoning although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. CONCLUSION: The ability of both novel bispyridinium oximes to decrease tabun-induced acute neurotoxicity was slightly lower than that of trimedoxime. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes such as trimedoxime in the treatment of acute tabun poisonings.

• Klíčová slova
• Functional observational battery, Neurotoxicity, Oximes, Rats, Tabun,
• MeSH
• antagonisté muskarinových receptorů farmakologie   MeSH
• atropin farmakologie   MeSH
• cholinesterasové inhibitory toxicita   MeSH
• krysa rodu Rattus MeSH
• nervový systém účinky léků   MeSH
• neuroprotektivní látky farmakologie   MeSH
• neurotoxické syndromy farmakoterapie   etiologie   MeSH
• organofosfáty toxicita   MeSH
• otrava organofosfáty farmakoterapie   etiologie   MeSH
• oximy farmakologie   MeSH
• potkani Wistar MeSH
• pyridinové sloučeniny farmakologie   MeSH
• reaktivátory cholinesterázy farmakologie   MeSH
• trimedoxim farmakologie   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
• 4-(ethylcarboxyl)-2'-(hydroxyiminomethyl)-1,1'-(phenylene-1,3-diyl)-bispyridinium MeSH Prohlížeč
• antagonisté muskarinových receptorů MeSH
• atropin MeSH
• cholinesterasové inhibitory MeSH
• naphthylene-2,7-diyl-bis(2-hydroxyiminomethylpyridinium) MeSH Prohlížeč
• neuroprotektivní látky MeSH
• organofosfáty MeSH
• oximy MeSH
• pyridinové sloučeniny MeSH
• reaktivátory cholinesterázy MeSH
• tabun MeSH Prohlížeč
• trimedoxim MeSH

The ability of two newly developed bispyridinium oximes (K456, K458) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with oxime K203 and trimedoxime using the functional observational battery. The neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose (200 μg/kg i.m.; 85% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by the functional observational battery and automatic measurement of motor activity at 2 hr after tabun challenge. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment. Both newly developed oximes (K456, K458) combined with atropine were able to decrease tabun-induced neurotoxicity in the case of sublethal poisonings although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to decrease tabun-induced acute neurotoxicity was slightly higher than that of trimedoxime and oxime K203, but the difference in neuroprotective efficacy among all oximes studied is not large enough to make a decision about replacement of commonly used oximes (especially trimedoxime and obidoxime) in the treatment of acute tabun poisonings.

• MeSH
• atropin farmakologie   MeSH
• chemické bojové látky toxicita   MeSH
• krysa rodu Rattus MeSH
• neuroprotektivní látky farmakologie   MeSH
• neurotoxické syndromy prevence a kontrola   MeSH
• organofosfáty toxicita   MeSH
• oximy farmakologie   MeSH
• potkani Wistar MeSH
• pyridinové sloučeniny farmakologie   MeSH
• trimedoxim 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
• 1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene MeSH Prohlížeč
• atropin MeSH
• chemické bojové látky MeSH
• K456 compound MeSH Prohlížeč
• K458 compound MeSH Prohlížeč
• neuroprotektivní látky MeSH
• organofosfáty MeSH
• oximy MeSH
• pyridinové sloučeniny MeSH
• tabun MeSH Prohlížeč
• trimedoxim MeSH