Oximes-induced reactivation of rat brain acetylcholinesterase inhibited by VX agent

A comparison of one mono- and seven bisquaternary acetylcholinesterase (AChE) reactivators of acetylcholinesterase inhibited by VX agent was performed. As a source of the acetylcholinesterase, a rat brain homogenate was taken. There were significant differences in reactivation potency of all tested oximes. The oxime TO205 seems to be the most efficacious followed by TO046, HI-6, HS-6, K027, obidoxime, MMC and 2-PAM. In addition, the results of this study showed that the reactivation potency of the tested reactivators depends on many factors-such as the number of pyridinium rings, the number of oxime groups and their position, as well as the length and the shape of linkage bridge between two pyridinium rings.

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A comparison of tabun-inhibited rat brain acetylcholinesterase reactivation by three oximes (HI-6, obidoxime, and K048) in vivo detected by biochemical and histochemical techniques

Journal of Enzyme Inhibition and Medicinal Chemistry ◽

10.3109/14756360903433373 ◽

2010 ◽

Vol 25 (6) ◽

pp. 790-797 ◽

Cited By ~ 3

Author(s):

Jiri Bajgar ◽

Petr Hajek ◽

Jana Karasova Zdarova ◽

Jiri Kassa ◽

Antonin Paseka ◽

...

Keyword(s):

Rat Brain ◽

Hi 6 ◽

Acetylcholinesterase Reactivation ◽

Brain Acetylcholinesterase

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In Vitro Potency of H Oximes (HI-6, HLö-7), the Oxime BI-6, and Currently Used Oximes (Pralidoxime, Obidoxime, Trimedoxime) to Reactivate Nerve Agent-Inhibited Rat Brain Acetylcholinesterase

Journal of Toxicology and Environmental Health Part A ◽

10.1080/15287390500364283 ◽

2006 ◽

Vol 69 (15) ◽

pp. 1431-1440 ◽

Cited By ~ 7

Author(s):

Kamil Kuca ◽

Jiri Cabal ◽

Jiri Kassa ◽

Daniel Jun ◽

Martina Hrabinova

Keyword(s):

Rat Brain ◽

Nerve Agent ◽

Hi 6 ◽

Hlö 7 ◽

Brain Acetylcholinesterase

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Bispyridinium Oximes As Antidotal Treatment of Cyclosarin Poisoning—In Vitro and In Vivo Testing

International Journal of Toxicology ◽

10.1080/10915810500366567 ◽

2005 ◽

Vol 24 (6) ◽

pp. 399-402 ◽

Cited By ~ 7

Author(s):

Lucie Bartosova ◽

Kamil Kuca ◽

Daniel Jun ◽

Gabriela Kunesova

Keyword(s):

Rat Brain ◽

Organophosphorus Compounds ◽

Brain Homogenate ◽

Chemical Structures ◽

Hi 6 ◽

In Vivo Testing ◽

Acetylcholinesterase Enzyme ◽

Enzyme Source

The mechanism of intoxication with organophosphorus compounds, including highly toxic nerve agents and less toxic pesticides, is based on the formation of irreversibly inhibited acetylcholinesterase, which causes cumulation of neuromediator acetylcholine in synaptic clefts and subsequent overstimulation of cholinergic receptors, that is followed by a generalized cholinergic crisis. Nerve agent poisoning is conventionally treated using a combination of a cholinolytic (atropine mostly) to counteract the accumulation of acetylcholine and acetylcholinesterase reactivators (pralidoxime or obidoxime) to reactivate inhibited acetylcholinesterase. In this study of cyclosarin poisoning treatment, oximes of different chemical structures (obidoxime, HI-6, BI-6, and HS-6) were tested in vitro on rat brain acetylcholinesterase (enzyme source: rat brain homogenate), and afterwards, they were tested in vivo in equimolar doses, in mice and rats. The HI-6 oxime appeared to be the most effective oxime in vitro and in vivo.

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A Comparison of the Potency of Newly Developed Oximes (K005, K027, K033, K048) and Currently Used Oximes (Pralidoxime, Obidoxime, HI-6) to Reactivate Sarin-Inhibited Rat Brain Acetylcholinesterase By in Vitro Methods

Journal of Toxicology and Environmental Health Part A ◽

10.1080/15287390590921784 ◽

2005 ◽

Vol 68 (8) ◽

pp. 677-686 ◽

Cited By ~ 18

Author(s):

Kamil Kuca ◽

Jiri Cabal ◽

Jiri Kassa

Keyword(s):

Rat Brain ◽

In Vitro Methods ◽

Hi 6 ◽

Brain Acetylcholinesterase

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Differential reactivation by HI-6 in vivo of paraoxon-inhibited rat brain acetylcholinesterase molecular forms

Neurochemistry International ◽

10.1016/0197-0186(94)00151-j ◽

1995 ◽

Vol 26 (4) ◽

pp. 347-350 ◽

Cited By ~ 9

Author(s):

J Bajgar

Keyword(s):

Rat Brain ◽

Molecular Forms ◽

Hi 6 ◽

Acetylcholinesterase Molecular Forms ◽

Brain Acetylcholinesterase

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A Comparison of the Potency of the Oxime HLö-7 and Currently Used Oximes (HI-6, Pralidoxime, Obidoxime) to Reactivate Nerve Agent-Inhibited Rat Brain Acetylcholinesterase by in vitro Methods

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2018.36 ◽

2005 ◽

Vol 48 (2) ◽

pp. 81-86 ◽

Cited By ~ 14

Author(s):

Kamil Kuča ◽

Jiří Cabal ◽

Jiří Kassa ◽

Daniel Jun ◽

Martina Hrabinová

Keyword(s):

Rat Brain ◽

Nerve Agents ◽

Nerve Agent ◽

The Other ◽

In Vitro Evaluation ◽

In Vitro Methods ◽

Hi 6 ◽

Hlö 7 ◽

Brain Acetylcholinesterase

1. The efficacy of the oxime HLö-7 and currently used oximes (pralidoxime, obidoxime, HI-6) to reactivate acetylcholinesterase inhibited by various nerve agents (sarin, tabun, cyclosarin, VX) was tested by in vitro methods. 2. Both H oximes (HLö-7, HI-6) were found to be more efficacious reactivators of sarin and VX-inhibited acetylcholinesterase than pralidoxime and obidoxime. On the other hand, their potency to reactivate tabun-inhibited acetylcholinesterase is very low and does not reach the reactivating efficacy of obidoxime. In the case of cyclosarin, the oxime HI-6 was only found to be able to sufficiently reactivate cyclosarin-inhibited acetylcholinesterase in vitro. 3. Thus, the oxime HLö-7 does not seem to be more efficacious reactivator of nerve agent-inhibited acetylcholinesterase than HI-6 according to in vitro evaluation of their reactivation potency and, therefore, it is not more suitable to be introduced for antidotal treatment of nerve agent-exposed people than HI-6.

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