Novel acetylcholinesterase reactivator K112 and its cholinergic properties
Language English Country France Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20634031
DOI
10.1016/j.biopha.2010.01.002
PII: S0753-3322(10)00003-X
Knihovny.cz E-resources
- MeSH
- Acetylcholinesterase metabolism MeSH
- Cholinesterase Inhibitors chemistry pharmacology MeSH
- Membrane Fluidity drug effects MeSH
- Hippocampus drug effects enzymology MeSH
- Muscle, Smooth drug effects enzymology MeSH
- Rats MeSH
- Urinary Bladder drug effects enzymology MeSH
- Organophosphate Poisoning MeSH
- Poisoning drug therapy enzymology MeSH
- Oximes chemistry pharmacology MeSH
- Rats, Sprague-Dawley MeSH
- Rats, Wistar MeSH
- Swine MeSH
- Pyridinium Compounds chemistry pharmacology MeSH
- Cholinesterase Reactivators chemistry pharmacology MeSH
- Receptor, Muscarinic M2 antagonists & inhibitors MeSH
- Recombinant Proteins antagonists & inhibitors MeSH
- Heart drug effects MeSH
- Heart Rate drug effects MeSH
- Muscle Contraction drug effects MeSH
- Synaptosomes drug effects enzymology MeSH
- In Vitro Techniques MeSH
- Protein Binding MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 4,4'-bis(hydroxyiminomethyl)-1,10-(1,2-phenylenedimethyl)bispyridinium MeSH Browser
- Acetylcholinesterase MeSH
- Cholinesterase Inhibitors MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- Cholinesterase Reactivators MeSH
- Receptor, Muscarinic M2 MeSH
- Recombinant Proteins MeSH
The oxime reactivator K112 is a member of the new group of xylene linker-containing AChE reactivators. Its cholinergic properties could be of importance at OP poisoning and are not related to the AChE reactivation that has been studied. It has been found that, despite of reactivating potency, this compound has additional effects. These cholinergic effects include a weak inhibition of AChE (IC(50)=43.8 ± 4.88 μM), inhibition of binding to the porcine muscarinic M2 receptor (IC(50)=4.36 μM) and finally, the inhibition of HACU (68.4 ± 9.9%), a key regulatory step in the synthesis of ACh. The inhibition of the binding of (3H)-HC-3 (64.7 ± 4.7%) and the influence on the membrane fluidity have also been observed. Blocking properties of K112 on the muscarinic receptors have been revealed in the in vitro experiment (rat urinary bladder) and in the in vivo experiment (rat heart BPM) as well. All these cholinergic properties could significantly contribute to the antidotal effect of K112 at the poisoning by the organophosphates.
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