Comparison of the potency of newly developed and currently available oximes to reactivate nerve agent-inhibited acetylcholinesterase in vitro and in vivo
ABSTRACT Reactivation potency of three newly developed oximes K027, K033 and K048 was tested using standard in vitro and in vivo reactivation tests. K027 and K048 seem to be efficacious reactivators of tabun-inhibited acetylcholinesterase. K033 is sufficient reactivator of cyclosarin-inhibited AChE. However, its potency is poor compared with current "gold standard" oxime HI-6.
SourceAvailable from: Ivan Samnaliev[Show abstract] [Hide abstract]
ABSTRACT: The most toxic warfare agents called nerve agents (tabun, sarin, soman, cyclosarin, VX) affect the peripheral and central nervous systems and others specific systems and organs as well. The respiratory system reacts to nerve agent poisoning with salivation, bronhorrhea, bronhospasm and centrally determined arrest. In the same conditions cardio vascular system reacts with bradycardia or tachycardia, cardiac arrhythmia, hypertension or hypotension and circulatory failure. The currently available antidote treatment of nerve agent intoxication consists of anticholinergic drug (atropine) and oxime cholinesterase reactivator. The goal of this study was to evaluate the ability of two newly synthesized reactivators of cholinesterase (BT-03 and BT-05) combined with atropine to abolish or minimize the toxic effects of soman and tabun on respiration, heart rate and blood pressure in rats. The survival time and rate of survival were determined as well. The results obtained showed that BT-05 had very positive influence on the soman and tabun-induced changes in respiration, hurt rate and circulation. BT-03 was ineffective against soman but at the same time ensured survival of all tabun poisoned animals. The antidote efficacy of the new synthesized compounds was compared to those of well known oxime reactivators obidoxime and HI-6.Military medicine 01/2009; Supplement(LXI):32-37. · 0.77 Impact Factor
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ABSTRACT: Description of the simple HPLC method with UV detection for the identification of the acetylcholinesterase reactivator–HI‐6 is described. Two salts of HI‐6 (dichloride and dimethanesulfonate) were tested. Using this method 0.5 µM LOD was determined. Our method could be used in future as standard method for the evaluation of HI‐6 stability and purity.Analytical Letters 10/2007; 40(14):2783-2787. DOI:10.1080/00032710701588531 · 0.98 Impact Factor
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ABSTRACT: This paper reviews the blood–brain barrier (BBB) penetration of newly developed pyridinium aldoximes. Pyridinium aldoximes are highly charged hydrophilic compounds used in the treatment of subjects exposed to organophosphonates because they are effective as acetylcholinesterase reactivators. Pyridinium aldoximes have antidotal effects against poisoning with cholinesterase inhibitors, a frequent problem affecting people working with organophosphate-based insecticides and pesticides. Toxic organophosphonate products such as sarin and tabun can be used by terrorists as chemical warfare agents. This poses a severe challenge to all innocent and peace-loving people worldwide. This review gives a brief summary of BBB transporters and description of the current in vitro and in vivo methods for the characterization of BBB penetration of established and novel pyridinium aldoximes. The authors provide a putative mechanism of penetration, outline some future ways of formulation and discuss the possible advantages and disadvantages of increasing BBB penetration. Copyright © 2014 John Wiley & Sons, Ltd.Journal of Applied Toxicology 02/2015; 35(2). DOI:10.1002/jat.3048 · 3.17 Impact Factor