Naslov
Oximes: reactivators of phosphorylated acetylcholinesterase and antidotes in therapy against tabun poisoning

Autori
Kovarik, Zrinka ; Čalić, Maja ; Šinko, Goran ; Bosak, Anita ; Berend, Suzana ; Lucić Vrdoljak, Ana ; Radić, Božica

Izvornik
Chemico-Biological Interactions (0009-2797) 175 (2008), 1-3 Special Issue; 173-179

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
antidote; bioscavenger; butyrylcholinesterase; nerve agents; pretreatment

Sažetak
One of the therapeutic approaches to organophosphate poisoning is to reactivate AChE with site-directed nucleophiles such as oximes. However, pyridinium oximes 2-PAM, HI-6, TMB-4 and obidoxime, found as the most effective reactivators, have limiting reactivating potency in tabun poisoning. We tested oximes varying in the type of ring (pyridinium and/or imidazolium), the length and type of the linker between rings, and in the position of the oxime group on the ring to find more effective oximes to reactivate tabun-inhibited human erythrocyte AChE. Three of our tested pyridinium oximes K027, K048, K074, along with TMB-4, were the most promising for AChE reactivation. Promising oximes were further tested in vivo on tabun poisoned mice not only as antidotes in combination with atropine but also as pretreatment drug. Herein we showed that a promising treatment in tabun poisoning by selected oximes and atropine could be improved if oximes are also used in pretreatment. Since the reactivating efficacy of the oximes in vitro corresponded to their therapeutic efficacy in vivo, it seems that pharmacological effect of these oximes is indeed primarily related to the reactivation of tabun-phosphorylated AChE.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

Napomena
Proceedings of the IX International Meeting on Cholinesterases ; Karl Tsim, Bhupendra Doctor (Eds.)

POVEZANOST RADA