Harris L W, Talbot B G, Lennox W J, Anderson D R
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Toxicol Appl Pharmacol. 1989 Mar 15;98(1):128-33. doi: 10.1016/0041-008x(89)90140-3.
The efficacy of the oximes pyridinium-2-aldoxime methochloride (2-PAM) and 1-[[[(4-aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydro xyimino) methyl]pyridinium dichloride (HI-6), in combination with atropine (At), against lethality by either carbaryl (CA) or physostigmine (Phy) was investigated in rats. The protection by At, 8 mg/kg, iv, against CA intoxication was reduced by 2-PAM (22 mg/kg, iv) and HI-6 (50 mg/kg, iv) from a protective ratio (PR) of 6.6 to 3.5 and 2.3, respectively. However, in Phy-intoxicated rats, the administration, iv, of At alone, At + 2-PAM, or At + HI-6 at 1 min following Phy provided good protection and resulted in PRs of 7.2, 8.8, and 23.3, respectively. In experiments on decarbamylation of inhibited acetylcholinesterase (AChE), HI-6 and 2-PAM accelerated (p less than 0.05) the decarbamylation of Phy-inhibited AChE in vitro, and HI-6 decreased (p less than 0.05) the inhibition of whole blood AChE in Phy-intoxicated rats. These findings show that the protection was increased substantially by the use of either 2-PAM or HI-6 against Phy-induced lethality, whereas the use of oximes against carbaryl poisoning was contraindicated. Furthermore, even though CA and Phy are both N-methyl carbamates, the data indicate that there is no adverse interaction between 2-PAM or HI-6 and Phy.
研究了肟类化合物氯解磷定（2-PAM）和双复磷（HI-6）与阿托品（At）联合使用对大鼠西维因（CA）或毒扁豆碱（Phy）致死作用的疗效。静脉注射8mg/kg阿托品对CA中毒的保护作用，因静脉注射2-PAM（22mg/kg）和HI-6（50mg/kg）而分别从保护率（PR）6.6降至3.5和2.3。然而，在Phy中毒的大鼠中，在Phy中毒后1分钟静脉注射单独的阿托品、阿托品+2-PAM或阿托品+HI-6均提供了良好的保护，保护率分别为7.2、8.8和23.3。在抑制的乙酰胆碱酯酶（AChE）脱氨基甲酰化实验中，HI-6和2-PAM在体外加速了（p<0.05）Phy抑制的AChE的脱氨基甲酰化，并且HI-6降低了（p<0.05）Phy中毒大鼠全血AChE的抑制作用。这些发现表明，使用2-PAM或HI-6可显著提高对Phy诱导的致死作用的保护，而使用肟类化合物对抗西维因中毒是禁忌的。此外，尽管CA和Phy都是N-甲基氨基甲酸酯类，但数据表明2-PAM或HI-6与Phy之间没有不良相互作用。
