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[乙酰胆碱酯酶复活剂剂量对其治疗小鼠塔崩中毒有效性的影响]

[Effect of acetylcholinesterase reactivator dosage on its effectiveness in the treatment of tabun poisoning in mice].

作者信息

Kassa J

机构信息

Vojenská lékarská akademie JEP, Hradec Králové.

出版信息

Ceska Slov Farm. 2004 Jan;53(1):31-4.

Abstract

The therapeutic efficacy of selected reactivators of acetylcholinesterase (obidoxime, oxime HI-6, trimedoxime) against acute tabun poisoning in dependence on their dose was examined in experiments on male mice. A comparison of the values of the medium lethal dose (LD50) of tabun in the intoxication influenced by an antidote therapy consisting of atropin and some of the oximes tested revealed that in all three oximes under study their dose markedly influenced their effect. The highest efficacy was always achieved when oximes were administered in the maximal therapeutic dose (20% of LD50). It follows from the comparison of the efficacy of equieffective doses of the oximes tested that in all doses the acute lethal effects of tabun are most effectively eliminated by trimedoxime, and on the other hand, obidoxime seems to be least effective, though in the smallest dose tested (2% of LD50) the differences between the therapeutic efficacy of the individual oximes are not statistically significant. Oxime HI-6 is significantly more effective than obidoxime (in a dose corresponding to 20% of LD50), but it is less effective than trimedoxime (in a dose corresponding to 5% LD50). The achieved results have shown that oxime HI-6, so effective against soman, another nerve agent, is not the most advantageous reactivator of acetylcholinesterase for the therapy of acute tabun poisonings, though its efficacy is partly eliminated by its possible higher dosing in human medicine due to its lower toxicity for mammals. The most suitable reactivator of acetylcholinesterase for the elimination of acute lethal toxic effects of tabun seems to be trimedoxime. Obidoxime, which is the most widely used reactivator of acetylcholinesterase in the therapy of poisonings by nerve agents at present, is, like in the case of soman poisonings, a relatively least suitable oxime ensuring the survival in lethal tabun poisonings.

摘要

在雄性小鼠实验中,研究了所选乙酰胆碱酯酶复活剂(双复磷、HI-6肟、三甲肟)对急性塔崩中毒的治疗效果及其剂量依赖性。比较在由阿托品和某些受试肟组成的解毒疗法影响下,中毒小鼠体内塔崩的半数致死剂量(LD50)值,结果显示,在所研究的三种肟中,其剂量对效果有显著影响。当肟以最大治疗剂量(LD50的20%)给药时,总能达到最高疗效。通过比较受试肟等效应剂量的疗效可知,在所有剂量下,三甲肟对塔崩急性致死效应的消除最为有效,另一方面,双复磷似乎效果最差,不过在最小测试剂量(LD50的2%)时,各肟治疗效果的差异无统计学意义。HI-6肟在对应LD50的20%剂量时比双复磷显著更有效,但在对应LD50的5%剂量时比三甲肟效果差。研究结果表明,对另一种神经毒剂梭曼非常有效的HI-6肟,并非治疗急性塔崩中毒最有利的乙酰胆碱酯酶复活剂,尽管因其对哺乳动物毒性较低,在人类医学中可能需更高剂量给药,但其疗效部分被抵消。消除塔崩急性致死毒性效应最合适的乙酰胆碱酯酶复活剂似乎是三甲肟。双复磷是目前神经毒剂中毒治疗中最广泛使用的乙酰胆碱酯酶复活剂,与梭曼中毒情况一样,在致死性塔崩中毒中是相对最不合适的肟,难以确保存活。

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