Hanke D W, Beckett M S, Overton M A, Burdick C K, Lieske C N
US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
J Appl Toxicol. 1990 Apr;10(2):87-91. doi: 10.1002/jat.2550100205.
The comparative potency of oximes for reactivation of inhibited eel acetylcholinesterase (AChE) in vitro is dependent on the organophosphinate inhibitor. Some of the data, dealing with a reference organophosphonate, support the conclusion of other investigators that the oxime potency order is also dependent on the inhibiting phosphonate. This work was done to identify more clearly the nature of phosphinylated AChE with regard to oxime reactivation potency and the potential of phosphinates as pretreatment drugs to protect AChE against organophosphonate poisoning. We have determined the reactivation potency of four oximes--2-PAM, HI-6, TMB-4 and toxogonin--against four phosphinates--4-nitrophenyl methyl(phenyl)phosphinate (PMP), 4-nitrophenyl chloromethyl(phenyl)phosphinate (CPMP), 4-nitrophenyl trifluoromethyl(phenyl)phosphinate and 4-nitrophenyl bis(2-thienyl)phosphinate. For comparison, the phosphonate sarin (GB, isopropyl methylphosphonofluoridate) was included. Incubation of the inhibited enzyme (I-AChE) at 25 degrees C was with 0.30 microM oxime for PMP, 3.0 microM oxime for sarin and CPMP and 100 microM oxime for the two remaining phosphinates. AChE activity was assayed spectrophotometrically for 3.0 min at 272.5 nm at 25 degrees C in 0.10 M MOPS buffer (pH 7.60) using phenyl acetate as substrate. When sarin was the inhibitor (0% spontaneous recovery after a 2-h incubation), the order of oxime reactivation was 2-PAM (46%) greater than or equal to toxogonin (33%) = TMB-4 (31%) greater than HI-6 (9%) after 2-h incubations. For PMP (12% spontaneous recovery after a 2-h incubation) the oxime order was toxogonin (67%) greater than TMB-4 (53%) greater than 2-PAM (40%) after 2-h incubations.(ABSTRACT TRUNCATED AT 250 WORDS)
在体外，肟类化合物使受抑制的鳗鱼乙酰胆碱酯酶（AChE）重新活化的相对效力取决于有机磷化物抑制剂。一些涉及参考有机膦酸酯的数据支持了其他研究者的结论，即肟类化合物的效力顺序也取决于抑制性膦酸酯。开展这项研究是为了更清楚地确定磷酰化AChE在肟类化合物重新活化效力方面的性质，以及有机磷化物作为预处理药物保护AChE免受有机膦酸酯中毒的潜力。我们测定了四种肟类化合物——2 - 解磷定（2 - PAM）、HI - 6、TMB - 4和双复磷——对四种有机磷化物——4 - 硝基苯基甲基（苯基）膦酸酯（PMP）、4 - 硝基苯基氯甲基（苯基）膦酸酯（CPMP）、4 - 硝基苯基三氟甲基（苯基）膦酸酯和4 - 硝基苯基双（2 - 噻吩基）膦酸酯的重新活化效力。为作比较，还纳入了有机膦酸酯沙林（GB，异丙基甲基膦酰氟）。在25℃下，使受抑制的酶（I - AChE）与0.30微摩尔/升的肟类化合物（用于PMP）、3.0微摩尔/升的肟类化合物（用于沙林和CPMP）以及100微摩尔/升的肟类化合物（用于其余两种有机磷化物）一起孵育。在25℃下，于0.10 M MOPS缓冲液（pH 7.60）中，以醋酸苯酯作为底物，在272.5纳米处用分光光度法测定AChE活性3.0分钟。当抑制剂为沙林时（孵育2小时后自发恢复率为0%），孵育2小时后肟类化合物重新活化的顺序为2 - PAM（46%）≥双复磷（33%） = TMB - 4（
