Specification of the structure of oximes able to reactivate tabun-inhibited acetylcholinesterase
Language English Country England, Great Britain Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
15379785
DOI
10.1111/j.1742-7843.2004.950207.x
PII: PTO950207
Knihovny.cz E-resources
- MeSH
- Acetylcholine metabolism MeSH
- Acetylcholinesterase drug effects physiology MeSH
- Phosphorylation MeSH
- Rats MeSH
- Quantitative Structure-Activity Relationship * MeSH
- Lethal Dose 50 MeSH
- Molecular Conformation * MeSH
- Organophosphates adverse effects antagonists & inhibitors metabolism MeSH
- Oximes chemistry metabolism pharmacology MeSH
- Rats, Wistar MeSH
- Drug Evaluation, Preclinical methods MeSH
- Pyridinium Compounds chemistry metabolism pharmacology 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
- Acetylcholine MeSH
- Acetylcholinesterase MeSH
- asoxime chloride MeSH Browser
- Organophosphates MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- tabun MeSH Browser
The efficacy of various oximes to reactivate acetylcholinesterase phosphorylated by tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) was tested by in vitro and in vivo methods. The oximes commonly used for the treatment of acute poisonings with highly toxic organophosphates appeared to be almost ineffective (HI-6, pralidoxime, methoxime) or just slightly effective (obidoxime) against tabun. On the other hand, trimedoxime seemed to be a significantly more efficacious reactivator than the others in the case of tabun poisonings. In vitro, the concentration of trimedoxime corresponding to 1.0 mmol/l was able to reach 50% reactivation of tabun-inhibited brain acetylcholinesterase. Higher reactivating potency of trimedoxime in comparison with the other commonly used oximes was demonstrated by in vivo method, too. In addition, other structural analogues of trimedoxime were found to be efficacious in counteracting tabun-induced acetylcholinesterase inhibition although not as efficacious as trimedoxime itself. Some effective acetylcholinesterase reactivators were characterised by dissociation constant of enzyme-reactivator complex as well as enzyme-inhibitor-reactivator complex and by rate constant of reactivation.
References provided by Crossref.org
Acetylcholinesterase: The "Hub" for Neurodegenerative Diseases and Chemical Weapons Convention
Reactivation of sarin-inhibited pig brain acetylcholinesterase using oxime antidotes
Reactivation of organophosphate-inhibited acetylcholinesterase by quaternary pyridinium aldoximes
