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Jiri Kassa - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the influence of three newly developed bispyridinium anti nicotinic compounds mb408 mb442 mb444 on the efficacy of antidotal treatment of nerve agent poisoning in mice
Basic & Clinical Pharmacology & Toxicology, 2018Co-Authors: Jiri Kassa, Christopher M Timperley, Mike Bird, Rebecca L Williams, Christopher A Green, John E H TattersallAbstract:The influence of three newly-developed bispyridinium antinicotinic compounds (the non-oximes MB408, MB442 and MB444) on the therapeutic efficacy of a standard antidotal treatment (atropine in combination with an oxime) of acute poisoning by the organophosphorus nerve agents Tabun and soman was studied in mice. The therapeutic efficacy of atropine in combination with an oxime with or without one of the bispyridinium non-oximes was evaluated by determination of the LD50 values of the nerve agents and measurement of the survival time after supralethal poisoning. Addition of all the tested non-oximes increased significantly the therapeutic efficacy of atropine in combination with an oxime against Tabun poisoning. They also positively influenced the number of surviving mice 6 hr after supralethal poisoning with Tabun. However, they were only slightly effective for the treatment of soman poisoning. The benefit of the tested bispyridinium non-oximes was dose-dependent. To conclude, the addition of bispyridinium non-oximes to the standard antidotal treatment of acute poisoning with Tabun was beneficial regardless of the chosen non-oxime, but only slightly beneficial in the case of soman poisoning. This article is protected by copyright. All rights reserved.
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The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats—A Comparison with Trimedoxime and the Oxime K203
MDPI AG, 2017Co-Authors: Jiri Kassa, Filip Caisberger, Jana Žďárová Karasová, Jana Hatlapatková, Jan Misik, Vendula Sepsova, Jaroslav PejchalAbstract: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
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a comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator kr 22934 with the oxime k203 and commonly used oximes obidoxime trimedoxime hi 6 in Tabun poisoned rats and mice
Toxicology Mechanisms and Methods, 2011Co-Authors: Jiri Kassa, Jiri Bajgar, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Růžena Pavlíková, Youngsik JungAbstract: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).
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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
Basic & Clinical Pharmacology & Toxicology, 2010Co-Authors: Jiri Kassa, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Sandra Tesarova, Youngsik JungAbstract: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 acetyl- cholinesterase-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 lg ⁄ kg intramuscularly (i.m.); 80% of LD50 value) were monitored by a functional observational battery at 24 hr after Tabun challenge. The results indicate that all tested oximes com- bined 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 symp- toms. 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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a comparison of reactivating and therapeutic efficacy of the oxime k203 and its fluorinated analog kr 22836 with currently available oximes obidoxime trimedoxime hi 6 against Tabun in rats and mice
Journal of Enzyme Inhibition and Medicinal Chemistry, 2010Co-Authors: Jiri Kassa, Filip Caisberger, Kamil Musilek, Youngsik JungAbstract:The potency of newly developed bispyridinium compound K203 and its fluorinated analog KR-22836 in reactivating Tabun-inhibited acetylcholinesterase and reducing Tabun-induced lethal toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determining the percentage of reactivation of Tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of K203 is higher than the reactivating efficacy of its fluorinated analog KR-22836 as well as currently available oximes studied. The therapeutic efficacy of the oxime K203 and its fluorinated analog corresponds to their potency to reactivate Tabun-inhibited acetylcholinesterase. According to the results, the oxime K203 is more suitable than KR-22836 for the replacement of commonly used oximes for the antidotal treatment of acute Tabun poisoning due to its relatively high potency to counteract the acute toxicity of Tabun.
Kamil Musilek - One of the best experts on this subject based on the ideXlab platform.
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A newly developed oxime K203 is the most effective reactivator of Tabun-inhibited acetylcholinesterase
BMC Pharmacology and Toxicology, 2018Co-Authors: Kamil Kuca, Daniel Jun, Kamil Musilek, Jana Zdarova-karasova, Eugenie Nepovimova, Ondrej Soukup, Martina Hrabinova, John Mikler, Tanos C. C. Franca, Elaine F. F. Da CunhaAbstract:Background Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of Tabun poisonings than currently fielded oximes. Methods To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6). Results Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant ( k _r) of 2142 min^− 1. M^− 1, which was 51 times higher than that obtained for obidoxime ( k _r = 42 min^− 1. M^− 1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate Tabun-inhibited human AChE. Discussion According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of Tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to Tabun exposure.
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comparison of the neuroprotective effects of a novel bispyridinium oxime kr 22934 with the oxime k203 and obidoxime in Tabun poisoned male rats
Journal of Applied Biomedicine, 2014Co-Authors: Jiří Kassa, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Youngsik JungAbstract:Summary The neuroprotective effects of a novel oxime KR-22934, the oxime K203 and obidoxime in combination with atropine in rats poisoned with Tabun at a sublethal dose (200 μg/kg i.m.; 80% LD 50 ) were studied. The Tabun-induced neurotoxicity was monitored at 24 h following Tabun challenge using a functional observational battery and an automatic measurement of motor activity. The results indicate that all Tabun-poisoned rats treated with oximes in combination with atropine were able to survive within 24 h following Tabun poisoning. One Tabun-poisoned rat without antidotal treatment died within 24 h. The oximes KR-22934 and K203 combined with atropine showed a similar potency to decrease Tabun-induced neurotoxicity at 24 h after Tabun administration while the neuroprotective efficacy of obidoxime was slightly higher. However, no oxime was able to eliminate Tabun-induced neurotoxicity completely. When atropine was administered alone, negligible neuroprotective efficacy was observed. Based on the results, a novel oxime KR-22934 did not bring any improvement of the neuroprotective efficacy of antidotal treatment of acute Tabun poisonings.
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a comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator kr 22934 with the oxime k203 and commonly used oximes obidoxime trimedoxime hi 6 in Tabun poisoned rats and mice
Toxicology Mechanisms and Methods, 2011Co-Authors: Jiri Kassa, Jiri Bajgar, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Růžena Pavlíková, Youngsik JungAbstract: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).
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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
Basic & Clinical Pharmacology & Toxicology, 2010Co-Authors: Jiri Kassa, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Sandra Tesarova, Youngsik JungAbstract: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 acetyl- cholinesterase-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 lg ⁄ kg intramuscularly (i.m.); 80% of LD50 value) were monitored by a functional observational battery at 24 hr after Tabun challenge. The results indicate that all tested oximes com- bined 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 symp- toms. 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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a comparison of reactivating and therapeutic efficacy of the oxime k203 and its fluorinated analog kr 22836 with currently available oximes obidoxime trimedoxime hi 6 against Tabun in rats and mice
Journal of Enzyme Inhibition and Medicinal Chemistry, 2010Co-Authors: Jiri Kassa, Filip Caisberger, Kamil Musilek, Youngsik JungAbstract:The potency of newly developed bispyridinium compound K203 and its fluorinated analog KR-22836 in reactivating Tabun-inhibited acetylcholinesterase and reducing Tabun-induced lethal toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determining the percentage of reactivation of Tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of K203 is higher than the reactivating efficacy of its fluorinated analog KR-22836 as well as currently available oximes studied. The therapeutic efficacy of the oxime K203 and its fluorinated analog corresponds to their potency to reactivate Tabun-inhibited acetylcholinesterase. According to the results, the oxime K203 is more suitable than KR-22836 for the replacement of commonly used oximes for the antidotal treatment of acute Tabun poisoning due to its relatively high potency to counteract the acute toxicity of Tabun.
Kamil Kuca - One of the best experts on this subject based on the ideXlab platform.
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A newly developed oxime K203 is the most effective reactivator of Tabun-inhibited acetylcholinesterase
BMC Pharmacology and Toxicology, 2018Co-Authors: Kamil Kuca, Daniel Jun, Kamil Musilek, Jana Zdarova-karasova, Eugenie Nepovimova, Ondrej Soukup, Martina Hrabinova, John Mikler, Tanos C. C. Franca, Elaine F. F. Da CunhaAbstract:Background Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of Tabun poisonings than currently fielded oximes. Methods To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6). Results Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant ( k _r) of 2142 min^− 1. M^− 1, which was 51 times higher than that obtained for obidoxime ( k _r = 42 min^− 1. M^− 1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate Tabun-inhibited human AChE. Discussion According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of Tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to Tabun exposure.
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comparison of the neuroprotective effects of a novel bispyridinium oxime kr 22934 with the oxime k203 and obidoxime in Tabun poisoned male rats
Journal of Applied Biomedicine, 2014Co-Authors: Jiří Kassa, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Youngsik JungAbstract:Summary The neuroprotective effects of a novel oxime KR-22934, the oxime K203 and obidoxime in combination with atropine in rats poisoned with Tabun at a sublethal dose (200 μg/kg i.m.; 80% LD 50 ) were studied. The Tabun-induced neurotoxicity was monitored at 24 h following Tabun challenge using a functional observational battery and an automatic measurement of motor activity. The results indicate that all Tabun-poisoned rats treated with oximes in combination with atropine were able to survive within 24 h following Tabun poisoning. One Tabun-poisoned rat without antidotal treatment died within 24 h. The oximes KR-22934 and K203 combined with atropine showed a similar potency to decrease Tabun-induced neurotoxicity at 24 h after Tabun administration while the neuroprotective efficacy of obidoxime was slightly higher. However, no oxime was able to eliminate Tabun-induced neurotoxicity completely. When atropine was administered alone, negligible neuroprotective efficacy was observed. Based on the results, a novel oxime KR-22934 did not bring any improvement of the neuroprotective efficacy of antidotal treatment of acute Tabun poisonings.
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a comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator kr 22934 with the oxime k203 and commonly used oximes obidoxime trimedoxime hi 6 in Tabun poisoned rats and mice
Toxicology Mechanisms and Methods, 2011Co-Authors: Jiri Kassa, Jiri Bajgar, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Růžena Pavlíková, Youngsik JungAbstract: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).
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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
Basic & Clinical Pharmacology & Toxicology, 2010Co-Authors: Jiri Kassa, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Sandra Tesarova, Youngsik JungAbstract: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 acetyl- cholinesterase-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 lg ⁄ kg intramuscularly (i.m.); 80% of LD50 value) were monitored by a functional observational battery at 24 hr after Tabun challenge. The results indicate that all tested oximes com- bined 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 symp- toms. 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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a comparison of neuroprotective efficacy of newly developed oximes k203 k206 and commonly used oximes obidoxime hi 6 in Tabun poisoned rats
Drug and Chemical Toxicology, 2009Co-Authors: Jiri Kassa, Jiri Bajgar, Jana Žďárová Karasová, Kamil Kuca, Libor Vasina, Kamil MusilekAbstract:The neuroprotective effects of newly developed oximes (K203, K206) and commonly used oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with Tabun at a sublethal dose (180 μg/kg i.m.; 80% LD50) were studied. The Tabun-induced neurotoxicity was monitored by using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of Tabun was monitored at 24 hours and 7 days following Tabun challenge. The results indicate that K203 and obidoxime in combination with atropine allow all Tabun-poisoned rats to survive within 7 days following Tabun challenge, while 2 nontreated Tabun-poisoned rats and 1 Tabun-poisoned rat treated with K206 or HI-6 in combination with atropine died within 7 days. Only one of the newly developed oximes (K203) combined with atropine seems to be effective for a decrease in Tabun-induced neurotoxicity within 24 hours after Tabun sublethal poisoning, although it is not able to eliminate Tabun-induced neurotoxicity completely. On th...
Jana Žďárová Karasová - One of the best experts on this subject based on the ideXlab platform.
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The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats—A Comparison with Trimedoxime and the Oxime K203
MDPI AG, 2017Co-Authors: Jiri Kassa, Filip Caisberger, Jana Žďárová Karasová, Jana Hatlapatková, Jan Misik, Vendula Sepsova, Jaroslav PejchalAbstract: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
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The Evaluation of the Potency of Newly Developed Oximes (K727, K733) and Trimedoxime to Counteract Acute Neurotoxic Effects of Tabun in Rats
Karolinum Press, 2016Co-Authors: Jiří Kassa, Jana Hatlapatková, Jana Žďárová KarasováAbstract: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
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comparison of the neuroprotective effects of a novel bispyridinium oxime kr 22934 with the oxime k203 and obidoxime in Tabun poisoned male rats
Journal of Applied Biomedicine, 2014Co-Authors: Jiří Kassa, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Youngsik JungAbstract:Summary The neuroprotective effects of a novel oxime KR-22934, the oxime K203 and obidoxime in combination with atropine in rats poisoned with Tabun at a sublethal dose (200 μg/kg i.m.; 80% LD 50 ) were studied. The Tabun-induced neurotoxicity was monitored at 24 h following Tabun challenge using a functional observational battery and an automatic measurement of motor activity. The results indicate that all Tabun-poisoned rats treated with oximes in combination with atropine were able to survive within 24 h following Tabun poisoning. One Tabun-poisoned rat without antidotal treatment died within 24 h. The oximes KR-22934 and K203 combined with atropine showed a similar potency to decrease Tabun-induced neurotoxicity at 24 h after Tabun administration while the neuroprotective efficacy of obidoxime was slightly higher. However, no oxime was able to eliminate Tabun-induced neurotoxicity completely. When atropine was administered alone, negligible neuroprotective efficacy was observed. Based on the results, a novel oxime KR-22934 did not bring any improvement of the neuroprotective efficacy of antidotal treatment of acute Tabun poisonings.
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a comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator kr 22934 with the oxime k203 and commonly used oximes obidoxime trimedoxime hi 6 in Tabun poisoned rats and mice
Toxicology Mechanisms and Methods, 2011Co-Authors: Jiri Kassa, Jiri Bajgar, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Růžena Pavlíková, Youngsik JungAbstract: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).
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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
Basic & Clinical Pharmacology & Toxicology, 2010Co-Authors: Jiri Kassa, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Sandra Tesarova, Youngsik JungAbstract: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 acetyl- cholinesterase-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 lg ⁄ kg intramuscularly (i.m.); 80% of LD50 value) were monitored by a functional observational battery at 24 hr after Tabun challenge. The results indicate that all tested oximes com- bined 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 symp- toms. 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.
Youngsik Jung - One of the best experts on this subject based on the ideXlab platform.
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comparison of the neuroprotective effects of a novel bispyridinium oxime kr 22934 with the oxime k203 and obidoxime in Tabun poisoned male rats
Journal of Applied Biomedicine, 2014Co-Authors: Jiří Kassa, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Youngsik JungAbstract:Summary The neuroprotective effects of a novel oxime KR-22934, the oxime K203 and obidoxime in combination with atropine in rats poisoned with Tabun at a sublethal dose (200 μg/kg i.m.; 80% LD 50 ) were studied. The Tabun-induced neurotoxicity was monitored at 24 h following Tabun challenge using a functional observational battery and an automatic measurement of motor activity. The results indicate that all Tabun-poisoned rats treated with oximes in combination with atropine were able to survive within 24 h following Tabun poisoning. One Tabun-poisoned rat without antidotal treatment died within 24 h. The oximes KR-22934 and K203 combined with atropine showed a similar potency to decrease Tabun-induced neurotoxicity at 24 h after Tabun administration while the neuroprotective efficacy of obidoxime was slightly higher. However, no oxime was able to eliminate Tabun-induced neurotoxicity completely. When atropine was administered alone, negligible neuroprotective efficacy was observed. Based on the results, a novel oxime KR-22934 did not bring any improvement of the neuroprotective efficacy of antidotal treatment of acute Tabun poisonings.
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a comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator kr 22934 with the oxime k203 and commonly used oximes obidoxime trimedoxime hi 6 in Tabun poisoned rats and mice
Toxicology Mechanisms and Methods, 2011Co-Authors: Jiri Kassa, Jiri Bajgar, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Růžena Pavlíková, Youngsik JungAbstract: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).
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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
Basic & Clinical Pharmacology & Toxicology, 2010Co-Authors: Jiri Kassa, Jana Žďárová Karasová, Kamil Kuca, Kamil Musilek, Sandra Tesarova, Youngsik JungAbstract: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 acetyl- cholinesterase-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 lg ⁄ kg intramuscularly (i.m.); 80% of LD50 value) were monitored by a functional observational battery at 24 hr after Tabun challenge. The results indicate that all tested oximes com- bined 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 symp- toms. 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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a comparison of reactivating and therapeutic efficacy of the oxime k203 and its fluorinated analog kr 22836 with currently available oximes obidoxime trimedoxime hi 6 against Tabun in rats and mice
Journal of Enzyme Inhibition and Medicinal Chemistry, 2010Co-Authors: Jiri Kassa, Filip Caisberger, Kamil Musilek, Youngsik JungAbstract:The potency of newly developed bispyridinium compound K203 and its fluorinated analog KR-22836 in reactivating Tabun-inhibited acetylcholinesterase and reducing Tabun-induced lethal toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determining the percentage of reactivation of Tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of K203 is higher than the reactivating efficacy of its fluorinated analog KR-22836 as well as currently available oximes studied. The therapeutic efficacy of the oxime K203 and its fluorinated analog corresponds to their potency to reactivate Tabun-inhibited acetylcholinesterase. According to the results, the oxime K203 is more suitable than KR-22836 for the replacement of commonly used oximes for the antidotal treatment of acute Tabun poisoning due to its relatively high potency to counteract the acute toxicity of Tabun.
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a comparison of the therapeutic and reactivating efficacy of newly developed oximes k117 k127 and currently available oximes obidoxime trimedoxime hi 6 in Tabun poisoned rats and mice
Drug and Chemical Toxicology, 2008Co-Authors: Jana Žďárová Karasová, Kamil Musilek, Youngsik JungAbstract:The potency of newly developed bispyridinium compounds (K117, K127) to reactivate Tabun-inhibited acetylcholinesterase and reduce Tabun-induced lethal toxic effects was compared with currently available oximes (obidoxime, trimedoxime, oxime HI-6) by using in vivo methods. A study that determined the percentage of reactivation of Tabun-inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of newly developed oxime K127 is comparable with obidoxime and trimedoxime in blood but lower than the reactivating potency of trimedoxime and obidoxime in the diaphragm and brain. The potency of another newly developed K117 to reactivate Tabun-inhibited acetylcholinesterase is comparable with obidoxime or trimedoxime in the diaphragm, but it is significantly lower than the reactivating potency of trimedoxime and obidoxime in the blood and brain. The oxime, K127, was also found to be relatively effective in reducing lethal toxic effects in Tabun-poisoned mice. Its therapeutic efficacy is consistent with the therapeutic potency of obidoxime. On the other hand, the potency of the oxime, K117, to reduce acute toxicity of Tabun is significantly lower compared to trimedoxime and obidoxime. The therapeutic efficacy of K117 and K127 corresponds to their potency to reactivate Tabun-inhibited acetylcholinesterase, especially in the diaphragm and brain. Contrary to obidoxime and trimedoxime, the oxime, HI-6, is not an effective oxime in the reactivation of Tabun-inhibited acetycholinesterase and in reducing the lethal effects of Tabun. The reactivating and therapeutic potency of both newly developed oximes does not prevail over the effectiveness of currently available obidoxime and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute Tabun poisoning.
