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.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- agonisté muskarinových receptorů farmakologie MeSH
- antagonisté muskarinových receptorů farmakologie MeSH
- chinuklidinylbenzilát metabolismus MeSH
- elektrická stimulace MeSH
- krysa rodu rattus MeSH
- oximy metabolismus farmakologie MeSH
- oxotremorin analogy a deriváty farmakologie MeSH
- potkani Wistar MeSH
- pyridinové sloučeniny metabolismus farmakologie MeSH
- reaktivátory cholinesterázy metabolismus farmakologie MeSH
- receptory muskarinové účinky léků MeSH
- receptory spřažené s G-proteiny metabolismus MeSH
- srdeční frekvence účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
