- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
The ability of four newly developed reversible inhibitors of acetylcholinesterase (PC-37, PC-48, JaKo 39, JaKo 40) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated and compared. No reversible inhibitor of acetylcholinesterase studied was able to decrease the LD50 value of soman in mice. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of acetylcholinesterase was not able to significantly protect mice against soman-induced lethal acute toxicity. In addition, neither pyridostigmine nor new reversible inhibitors of acetylcholinesterase was able to increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of acetylcholinesterase is not promising.
- MeSH
- antidota terapeutické užití MeSH
- cholinesterasové inhibitory terapeutické užití MeSH
- LD50 MeSH
- myši MeSH
- piperaziny terapeutické užití MeSH
- pyridostigmin-bromid terapeutické užití MeSH
- soman antagonisté a inhibitory otrava MeSH
- takrin analogy a deriváty terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
The potency of the oxime HI-6 and two combinations of oximes (HI-6 + trimedoxime, HI-6 + K203) to reduce sarin-induced acute neurotoxic signs and symptoms was evaluated in this study. Sarin-induced neurotoxicity and the neuroprotective effects of atropine alone or in combination with HI-6 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with sarin at a sublethal dose (108 μg/kg i.m.; 90% of LD(50) value) were monitored by a functional observatory battery (FOB) 24 h following sarin administration. The results indicate that both mixtures of oximes combined with atropine were able to survive sarin-poisoned rats 24 h following sarin administration while two non-treated sarin-poisoned rats and one sarin-poisoned rat treated with atropine alone or with atropine in combination with the oxime HI-6 died within 24 h following sarin poisoning. All types of antidotal treatment were able to decrease sarin-induced neurotoxic signs and symptoms but not completely. While atropine alone and atropine in combination with the oxime HI-6 were able to eliminate some sarin-induced neurotoxic signs and symptoms, the neuroprotective efficacy of both combinations of oximes with atropine was slightly higher. Thus, both tested combinations of oximes in combination with atropine bring a small benefit for the neuroprotective efficacy of antidotal treatment of acute sarin poisonings.
- MeSH
- antidota aplikace a dávkování terapeutické užití MeSH
- atropin chemie MeSH
- chemické bojové látky otrava toxicita MeSH
- cholinesterasové inhibitory otrava toxicita MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu rattus MeSH
- molekulární struktura MeSH
- neuroprotektivní látky terapeutické užití MeSH
- oximy aplikace a dávkování chemie terapeutické užití MeSH
- potkani Wistar MeSH
- pyridinové sloučeniny aplikace a dávkování chemie terapeutické užití MeSH
- reaktivátory cholinesterázy aplikace a dávkování terapeutické užití MeSH
- sarin otrava toxicita MeSH
- trimedoxim aplikace a dávkování chemie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The neuroprotective effects of a newly developed oxime K203 and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with sarin were studied. The sarin-induced neurotoxicity was monitored using a functional observatory battery at 2 hr after sarin challenge. The results indicate that the potency of a novel bispyridinium oxime K203 to counteract sarin-induced neurotoxicity is relatively low and roughly corresponds to the neuroprotective efficacy of obidoxime. Among tested oximes, the oxime HI-6 seems to be significanlty more efficacious to counteract acute neurotoxicity of sarin than commonly used obidoxime and a newly developed oxime K203. Thus, the oxime K203 does not provide any beneficial effect for the antidotal treatment of acute poisoning with sarin in comparison with the oxime HI-6 that should be considered to be the best oxime for antidotal treatment of acute sarin poisonings.
- MeSH
- antagonisté muskarinových receptorů terapeutické užití MeSH
- antidota škodlivé účinky terapeutické užití MeSH
- atropin terapeutické užití MeSH
- autonomní nervový systém účinky léků patofyziologie MeSH
- chemické bojové látky chemie toxicita MeSH
- cholinesterasové inhibitory chemie toxicita MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu rattus MeSH
- LD50 MeSH
- neurony účinky léků MeSH
- neurotoxické syndromy farmakoterapie patofyziologie MeSH
- obidoxim chlorid škodlivé účinky terapeutické užití MeSH
- oximy škodlivé účinky terapeutické užití MeSH
- potkani Wistar MeSH
- psychomotorický výkon účinky léků MeSH
- pyridinové sloučeniny škodlivé účinky terapeutické užití MeSH
- reaktivátory cholinesterázy škodlivé účinky terapeutické užití MeSH
- sarin antagonisté a inhibitory toxicita 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
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
The potency of bispyridinium acetylcholinesterase reactivator KR-22934 in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with the oxime K203 and commonly used oximes. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of KR-22934 was slightly higher than the reactivating efficacy of K203 and roughly corresponded to the reactivating efficacy of obidoxime and trimedoxime in blood and diaphragm. On the other hand, the oxime KR-22934 was not able to reactivate tabun-inhibited acetylcholinesterase in the brain. The therapeutic efficacy of all oximes studied approximately corresponded to their reactivating efficacy. Based on the results, one can conclude that the oxime KR-22934 is not suitable for the replacement of commonly used oximes for the antidotal treatment of tabun poisoning in spite of its potency to reactivate tabun-inhibited acetylcholinesterase in the peripheral compartment (blood, diaphragm).
- MeSH
- acetylcholinesterasa metabolismus MeSH
- antidota farmakologie terapeutické užití MeSH
- cholinesterasové inhibitory toxicita MeSH
- krysa rodu rattus MeSH
- myši MeSH
- obidoxim chlorid farmakologie terapeutické užití MeSH
- organofosfáty toxicita MeSH
- otrava farmakoterapie MeSH
- oximy farmakologie terapeutické užití MeSH
- potkani Wistar MeSH
- pyridinové sloučeniny farmakologie terapeutické užití MeSH
- reaktivátory cholinesterázy farmakologie terapeutické užití MeSH
- trimedoxim farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
