The effect of oxime reactivators on muscarinic receptors: functional and binding examinations.

O Soukup, U K Kumar, J Proska, L Bratova, A Adem, D Jun, J Fusek, K Kuca, G Tobin

文献索引：Environ. Toxicol. Pharmacol. 31(3) , 364-70, (2011)

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摘要

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.Copyright © 2011 Elsevier B.V. All rights reserved.