Therapeutic and reactivating efficacy of oximes K027 and K203 against a direct acetylcholinesterase inhibitor
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F16%3A10325227" target="_blank" >RIV/00179906:_____/16:10325227 - isvavai.cz</a>
Alternative codes found
RIV/62690094:18470/16:50004748
Result on the web
<a href="http://dx.doi.org/10.1016/j.neuro.2016.05.006" target="_blank" >http://dx.doi.org/10.1016/j.neuro.2016.05.006</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.neuro.2016.05.006" target="_blank" >10.1016/j.neuro.2016.05.006</a>
Alternative languages
Result language
angličtina
Original language name
Therapeutic and reactivating efficacy of oximes K027 and K203 against a direct acetylcholinesterase inhibitor
Original language description
As oxime-based structures are the only causal antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE), the majority of studies on these have been directed towards their synthesis and testing. In this study, experimental bispyridinium oximes K027 and K203, which have shown promising results in the last decade of research, were examined in vivo for their therapeutic and reactivating ability in acute poisoning by the direct AChE-inhibitor dichlorvos (DDVP), used as a dimethyl OP structural model. Additionally, the efficacy of oximes K027 and K203 was compared with the efficacy of four oximes (pralidoxime, trimedoxime, obidoxime and HI-6), already used in efficacy experiments and human medicine. To evaluate therapeutic efficacy, groups of Wistar rats were treated with equitoxic doses of oximes (5% LD50, i.m.) and/or atropine (10 mg/kg, i.m.) immediately after s.c. DDVP challenge (4-6 doses). Using the same antidotal protocol, AChE activity was measured in erythrocytes, diaphragm and brain 60 min after s.c. DDVP exposure (75% LD50). The oxime K027 was the most efficacious in reducing the DDVP induced lethal effect in rats, while the oxime K203 was more efficacious than trimedoxime, pralidoxime and HI-6. Significant reactivation of DDVP inhibited AChE was achieved only with oxime K027 or its combination with atropine in erythocytes and the diaphragm. Moreover, the acute i.m. toxicity of oxime K027 in rats was lower than all other tested oximes. The results of this study support previous studies considering the oxime K027 as a promising experimental oxime structure for further testing against structurally-different OP compounds.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Result continuities
Project
<a href="/en/project/GA15-16701S" target="_blank" >GA15-16701S: Concept of non-quaternary reactivators AChE as the antidotes of organophsophorus poisoning - a new hope or a blind way?</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
NeuroToxicology
ISSN
0161-813X
e-ISSN
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Volume of the periodical
55
Issue of the periodical within the volume
July
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
7
Pages from-to
33-39
UT code for WoS article
000380385800005
EID of the result in the Scopus database
2-s2.0-84969560264