A comparison of reactivating efficacy of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in cyclosarin-and tabun-poisoned rats
Language English Country England, Great Britain Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Antidotes chemistry pharmacology MeSH
- Butanes chemistry pharmacology MeSH
- Rats MeSH
- Brain drug effects enzymology MeSH
- Obidoxime Chloride chemistry pharmacology MeSH
- Organophosphates antagonists & inhibitors MeSH
- Organophosphorus Compounds antagonists & inhibitors MeSH
- Organophosphate Poisoning MeSH
- Oximes chemistry pharmacology MeSH
- Rats, Wistar MeSH
- Drug Evaluation, Preclinical MeSH
- Pyridinium Compounds chemistry pharmacology MeSH
- Cholinesterase Reactivators chemistry pharmacology MeSH
- Structure-Activity Relationship 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
- Names of Substances
- 1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide MeSH Browser
- Antidotes MeSH
- asoxime chloride MeSH Browser
- Butanes MeSH
- cyclohexyl methylphosphonofluoridate MeSH Browser
- K075 compound MeSH Browser
- Obidoxime Chloride MeSH
- Organophosphates MeSH
- Organophosphorus Compounds MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- Cholinesterase Reactivators MeSH
- tabun MeSH Browser
The potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, HI-6) to reactivate nerve agent-inhibited acetylcholinesterase was evaluated in rats poisoned with tabun or cyclosarin at a lethal dose corresponding to the LD50 value. In vivo determined percentage of reactivation of tabun-inhibited blood and brain acetylcholinesterase showed that obidoxime is the most efficacious reactivator of tabun-inhibited acetylcholinesterase among studied oximes in the peripheral compartment (blood) although the differences between obidoxime and newly developed oximes were not significant. On the other hand, one of the newly developed oximes (K074) seems to be a significantly more efficacious reactivator of tabun-inhibited acetylcholinesterase in the central compartment (brain) than the other studied oximes. In addition, the oxime HI-6 is unable to sufficiently reactivate tabun-inhibited acetylcholinesterase in rats. In vivo determined percentage of reactivation of cyclosarin-inhibited blood and brain acetylcholinesterase in poisoned rats showed that HI-6 is the most efficacious reactivator of cyclosarin-inhibited acetylcholinesterase among the studied oximes in the peripheral (blood) as well as central (brain) compartment although the differences between the oxime HI-6 and other tested oximes in the brain were not significant. Due to their reactivating effects, both newly developed K-oximes can be considered to be promising oximes for the antidotal treatment of acute tabun poisoning while the oximes HI-6 is still the most promising oxime for the treatment of acute cyclosarin poisonings due to its high potency in reactivating cyclosarin-inhibited acetylcholinesterase in the peripheral as well as central compartment.
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