The effect of oxime reactivators on muscarinic receptors: functional and binding examinations
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21787706
DOI
10.1016/j.etap.2011.01.003
PII: S1382-6689(11)00007-X
Knihovny.cz E-resources
- MeSH
- Acetylcholinesterase metabolism MeSH
- Muscarinic Agonists pharmacology MeSH
- Muscarinic Antagonists pharmacology MeSH
- Quinuclidinyl Benzilate metabolism MeSH
- Electric Stimulation MeSH
- Rats MeSH
- Oximes metabolism pharmacology MeSH
- Oxotremorine analogs & derivatives pharmacology MeSH
- Rats, Wistar MeSH
- Pyridinium Compounds metabolism pharmacology MeSH
- Cholinesterase Reactivators metabolism pharmacology MeSH
- Receptors, Muscarinic drug effects MeSH
- Receptors, G-Protein-Coupled metabolism MeSH
- Heart Rate drug effects 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
- Acetylcholinesterase MeSH
- Muscarinic Agonists MeSH
- Muscarinic Antagonists MeSH
- asoxime chloride MeSH Browser
- Quinuclidinyl Benzilate MeSH
- Oximes MeSH
- Oxotremorine MeSH
- oxotremorine M MeSH Browser
- Pyridinium Compounds MeSH
- Cholinesterase Reactivators MeSH
- Receptors, Muscarinic MeSH
- Receptors, G-Protein-Coupled MeSH
The antidotal treatment of organophosphorus poisoning is still a problematic issue since no versatile antidote has been developed yet. In our study, we focused on an interesting property, which does not relate to the reactivation of inhibited acetylcholinesterase (AChE) of some oximes, but refers to their anti-muscarinic effects which may contribute considerably to their treatment efficacy. One standard reactivator (HI-6) and two new compounds (K027 and K203) have been investigated for their antimuscarinic properties. Anti-muscarinic effects were studies by means of an in vitro stimulated atrium preparation (functional test), the [(3)H]-QNB binding assay and G-protein coupled receptor assay (GPCR, beta-Arrestin Assay). Based on the functional data HI-6 demonstrates the highest anti-muscarinic effect. However, only when comparing [(3)H]-QNB binding results and GPCR data, K203 shows a very promising compound with regard to anti-muscarinic potency. The therapeutic impact of these findings has been discussed.
References provided by Crossref.org
A-series agent A-234: initial in vitro and in vivo characterization
