Premium
A comparison of the potency of newly developed oximes (K027, K048) and commonly used oximes (obidoxime, HI‐6) to counteract tabun‐induced neurotoxicity in rats
Author(s) -
Kassa Jiří,
Kunesova Gabriela
Publication year - 2006
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1137
Subject(s) - tabun , atropine , neurotoxicity , oxime , chemistry , pharmacology , antidote , neuroprotection , anesthesia , nerve agent , medicine , toxicity , acetylcholinesterase , medicinal chemistry , biochemistry , organic chemistry , enzyme
The neuroprotective effects of newly developed oximes (K027, K048) and currently available oximes (obidoxime, HI‐6) in combination with atropine in rats poisoned with tabun at a sublethal dose (170 µg kg −1 i.m.; 80% of LD 50 value) were studied. The tabun‐induced neurotoxicity was monitored using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24 h and 7 days following tabun challenge. The results indicate that the oxime HI‐6 in combination with atropine was not able to protect the rats from the lethal effects of tabun. Two non‐treated tabun‐poisoned rats and one tabun‐poisoned rat treated with atropine combined with HI‐6 died within 2 h. On the other hand, all other tested oximes combined with atropine allowed all the tabun‐poisoned rats to survive 7 days following tabun challenge. Both newly developed oximes combined with atropine seem to be sufficiently effective antidotes for a decrease in tabun‐induced neurotoxicity in the case of sublethal poisoning although they are not able to eliminate tabun‐induced neurotoxicity completely. The neuroprotective efficacy of obidoxime in combination with atropine approached the potency of newly developed oximes but the ability of the oxime HI‐6 to counteract tabun‐induced acute neurotoxicity was significantly lower, especially at 24 h after tabun poisoning. Due to their neuroprotective effects, both newly developed oximes appear to be suitable oximes for the antidotal treatment of acute tabun poisoning. Copyright © 2006 John Wiley & Sons, Ltd.