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A comparison of neuroprotective efficacy of the oxime K203 and its fluorinated analogue (KR-22836) with obidoxime in Tabun-poisoned rats
J. Kassa, JZ. Karasova, S. Tesarova, K. Musilek, K. Kuca, YS. Jung,
Language English Country Denmark
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
NLK
Medline Complete (EBSCOhost)
from 2004-01-01 to 1 year ago
Wiley Online Library (archiv)
from 1997-01-01 to 2012-12-31
- MeSH
- Acute Disease MeSH
- Autonomic Nervous System drug effects MeSH
- Chemical Warfare Agents poisoning MeSH
- Behavior, Animal drug effects MeSH
- Hyperkinesis chemically induced prevention & control MeSH
- Rats MeSH
- Molecular Structure MeSH
- Neuroprotective Agents administration & dosage chemistry therapeutic use MeSH
- Neurotoxicity Syndromes etiology prevention & control MeSH
- Obidoxime Chloride administration & dosage chemistry therapeutic use MeSH
- Organophosphates MeSH
- Organophosphate Poisoning MeSH
- Oximes administration & dosage chemistry therapeutic use MeSH
- Rats, Wistar MeSH
- Pyridinium Compounds administration & dosage chemistry therapeutic use MeSH
- Muscle Tonus drug effects MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
The ability of the newly developed bispyridinium compound K203 and its fluorinated analogue KR-22836 to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the currently available reactivator of acetylcholinesterase-obidoxime. Tabun-induced neurotoxicity and the neuroprotective effects of all tested oximes in combination with atropine in rats poisoned with tabun at a sublethal dose (200 μg/kg intramuscularly (i.m.); 80% of LD(50) value) were monitored by a functional observational battery at 24 hr after tabun challenge. The results indicate that all tested oximes combined with atropine were able to survive tabun-poisoned rats 24 hr after tabun challenge while one non-treated tabun-poisoned rat died within 24 hr after tabun poisoning. All tested oximes combined with atropine were able to decrease tabun-induced neurotoxicity in the case of sublethal poisoning but they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. While the ability to reduce tabun-induced acute neurotoxicity of obidoxime and K203 was similar, the neuroprotective efficacy of KR-22836 was slightly higher compared to other tested oximes. Thus, the newly developed fluorinated analogue of K203, called KR-22836, is able to slightly increase the neuroprotective effectiveness of antidotal treatment of acute tabun poisonings compared to K203 and currently available obidoxime.
Center of Advanced Studies Faculty of Military Health Sciences Hradec Kralove Czech Republic
Department of Toxicology Faculty of Military Health Sciences Hradec Kralove Czech Republic
Department of Toxicology Hradec Kralove Czech Republic
Medicinal Science Division Korea Research Institute of Chemical Technology Yusong Daejeon Korea
The 7th Field Hospital of the Czech Army Hradec Kralove Czech Republic
References provided by Crossref.org
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- $a The ability of the newly developed bispyridinium compound K203 and its fluorinated analogue KR-22836 to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the currently available reactivator of acetylcholinesterase-obidoxime. Tabun-induced neurotoxicity and the neuroprotective effects of all tested oximes in combination with atropine in rats poisoned with tabun at a sublethal dose (200 μg/kg intramuscularly (i.m.); 80% of LD(50) value) were monitored by a functional observational battery at 24 hr after tabun challenge. The results indicate that all tested oximes combined with atropine were able to survive tabun-poisoned rats 24 hr after tabun challenge while one non-treated tabun-poisoned rat died within 24 hr after tabun poisoning. All tested oximes combined with atropine were able to decrease tabun-induced neurotoxicity in the case of sublethal poisoning but they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. While the ability to reduce tabun-induced acute neurotoxicity of obidoxime and K203 was similar, the neuroprotective efficacy of KR-22836 was slightly higher compared to other tested oximes. Thus, the newly developed fluorinated analogue of K203, called KR-22836, is able to slightly increase the neuroprotective effectiveness of antidotal treatment of acute tabun poisonings compared to K203 and currently available obidoxime.
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