TY - JOUR
T1 - The effect of oxime reactivators on muscarinic receptors
T2 - Functional and binding examinations
AU - Soukup, O.
AU - Kumar, U. K.
AU - Proska, J.
AU - Bratova, L.
AU - Adem, A.
AU - Jun, D.
AU - Fusek, J.
AU - Kuca, K.
AU - Tobin, G.
N1 - Funding Information:
This work was supported by the grant of Ministry of Defense (Czech Republic) No. FVZ0000604 and Grant Agency Czech Republic P303/11/1907.
PY - 2011/5
Y1 - 2011/5
N2 - 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 [ 3H]-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 [ 3H]-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.
AB - 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 [ 3H]-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 [ 3H]-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.
KW - Beta-Arrestin
KW - Binding study
KW - Isolated atria
KW - Muscarinic receptors
KW - Organophosphates
KW - Reactivator
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U2 - 10.1016/j.etap.2011.01.003
DO - 10.1016/j.etap.2011.01.003
M3 - Article
C2 - 21787706
AN - SCOPUS:79954831997
SN - 1382-6689
VL - 31
SP - 364
EP - 370
JO - Environmental Toxicology and Pharmacology
JF - Environmental Toxicology and Pharmacology
IS - 3
ER -