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Evaluation of the Potency of Two Novel Bispyridinium Oximes ( K 456, K 458) in Comparison with Oxime K 203 and Trimedoxime to Counteract Tabun‐Induced Neurotoxicity in Rats
Author(s) -
Kassa Jiri,
Misik Jan,
Karasova Jana Z.
Publication year - 2013
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12083
Subject(s) - tabun , neurotoxicity , oxime , atropine , pharmacology , chemistry , neuroprotection , potency , anesthesia , medicine , nerve agent , toxicity , acetylcholinesterase , biochemistry , organic chemistry , in vitro , enzyme
The ability of two newly developed bispyridinium oximes ( K 456, K 458) to reduce tabun‐induced acute neurotoxic signs and symptoms was compared with oxime K 203 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 LD 50 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 ( K 456, K 458) 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 K 203, 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.