The antidotal efficacy of the bispyridinium oximes K027 and TMB-4 against tabun poisoning in mice (CROSBI ID 159963)
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Berend, Suzana ; Radić, Božica ; Kuča, Kamil ; Lucić Vrdoljak, Ana
engleski
The antidotal efficacy of the bispyridinium oximes K027 and TMB-4 against tabun poisoning in mice
A toxic effect of highly toxic nervous agents is irreversible inhibition of vitally important enzyme acethylcholinesterase (AChE). Inhibition of AChE results in accumulation of acetylcholine (ACh) at the synaptic cleft of the cholinergic neurons, leading to overstimulation of cholinergic receptors. The highly toxic nature of tabun has been known for many years, but there are still serious limitations to the antidotal therapy. In this paper a bispyridinium compound K027 [1-(4-hydroxyiminomethylpyridinium)-3-(-4-carbamoylpyridinium) propane dibromide] was tested as potential antidote in tabun poisoned mice. Oxime TMB-4 was included for comparison. The therapeutic efficacy of applied antidotal regimens was tested as pretreatment given 15 min before tabun poisoning and/or as therapy given 1 min after tabun poisoning. Using oxime K027 (25% of its LD50) plus atropine as both, pretreatment and therapy, we showed that this combination can protect mice 8 times better than the therapy alone. Under these experimental conditions we confirmed good antidotal efficacy of K027. Moreover, its low acute toxicity is as much as beneficial effect in contrast to high toxicity of currently used TMB-4.
Nerve agent; Tabun; Antidote; K027; TMB-4; Pretreatment; Therapy
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Povezanost rada
Temeljne medicinske znanosti