一些mono -和bisquaternary铵化合物的reactivatability soman-inhibited人类的乙酰胆碱酯酶体外。
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Hallek M, Szinicz L
一些mono -和bisquaternary铵化合物的reactivatability soman-inhibited人类的乙酰胆碱酯酶体外。
生物化学杂志。1988年3月1日,37 (5):819 - 25。
- PubMed ID
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3345199 (在PubMed]
- 文摘
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乙酰胆碱酯酶(疼痛)被有机磷索曼(1、2、2-trimethyl-propylmethylphosphonofluoridate)迅速成为抗活化soman-enzyme肟由于脱烷基化作用的复杂。这种反应被称为衰老。四mono的影响——bisquaternary铵化合物tetramethylammonium (TMA),六甲铵,十烃和琥珀胆碱reactivatability soman-inhibited,随着疼痛从人类红细胞体外研究。所有化合物可逆抑制剂的疼痛;各自的离解常数和抑制的类型表现出相当大的差异。这两个活动的亲和力和琥珀胆碱的别构部位是相当高的(81.3 microM冢;Ki 15.9 microM)和十烃(冢15.4 microM;Ki 4.4 microM)比TMA(冢1毫米;Ki 289.6 microM)和六甲铵(冢4.5毫米;Ki 331.8 microM)。 The reactivation experiments were performed in a four-step procedure (soman-inhibition at 0 degree and pH 10, aging at 37 degrees and pH 7.3, reactivation by the oxime HI 6 at 37 degrees and pH 7.3 followed by AChE assay). After these four steps (total duration 55 min), AChE was inhibited by soman to 95-100%. HI 6 could reactivate about 20% of the inhibited enzyme. All effectors increased the AChE reactivatability by HI 6 when added before aging was started. The maximal increase in reactivatability was higher in the presence of 1.6 mM suxamethonium (+35.8%) and 150 microM decamethonium (+40%) than of 22 mM TMA (+22.5%) and 8.3 mM hexamethonium (+19.2%). If the effectors were added after 5 min of aging they increased the activity of soman-inhibited AChE, but to a considerably smaller extent than HI 6. A good correlation of the respective Kii values and the effective concentrations of these drugs was observed, indicating that an allosteric binding site of AChE might be involved in the protective effect of these drugs.