Danilov A F, Grigoriev V M, Prokhorenko N K, Sherstobitov O E
Laboratory of Pharmacology, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St-Petersburg.
Eur J Pharmacol. 1995 Apr 13;277(1):15-9. doi: 10.1016/0014-2999(95)00041-i.
The action of the alkylating derivative of hexadecamethonium on frog neuromuscular transmission was studied with the help of intracellular microelectrodes. Treatment of frog m. cutaneous pectoris-n. pectoralis preparations with the alkylating derivative of hexadecamethonium (0.5 microM) for 30 min led to an irreversible decrease in the amplitude of the end-plate potentials by 2.5-fold without a change of their latency period or quantal content. Such treatment led also to a considerable reduction of the anticholinesterase effects of neostigmine and of the organophosphorus irreversible inhibitor, armine. Thus, when applied to intact nerve-muscle preparations, neostigmine (2 microM) or armine (1 microM) increased the amplitude of end-plate potentials by 80-90%, and the rise time and half-decay time by about 2- to 3-fold. However, after the nerve-muscle preparations were pretreated with the alkylating derivative of hexadecamethonium (0.5 microM, for 30 min), the amplitude of end-plate potentials increased by 20-25%, rise time by 15-20% and half-decay time by 40-50% only. Investigation of muscle acetylcholinesterase activity, using the Ellman technique, showed that the alkylating derivative of hexadecamethonium diminished the sensitivity of the muscle acetylcholinesterase to inhibition without exerting its own inhibitory action.
借助细胞内微电极研究了十六烷基三甲基溴化铵的烷基化衍生物对青蛙神经肌肉传递的作用。用十六烷基三甲基溴化铵的烷基化衍生物（0.5微摩尔）处理青蛙胸皮肌-胸神经制备物30分钟，导致终板电位幅度不可逆地降低2.5倍，而其潜伏期或量子含量没有变化。这种处理还导致新斯的明和有机磷不可逆抑制剂阿明的抗胆碱酯酶作用显著降低。因此，当应用于完整的神经肌肉制备物时，新斯的明（2微摩尔）或阿明（1微摩尔）使终板电位幅度增加80-90%，上升时间和半衰期增加约2至3倍。然而，在用十六烷基三甲基溴化铵的烷基化衍生物（0.5微摩尔，处理30分钟）预处理神经肌肉制备物后，终板电位幅度仅增加20-25%，上升时间增加15-20%，半衰期增加40-50%。使用埃尔曼技术对肌肉乙酰胆碱酯酶活性的研究表明，十六烷基三甲基溴化铵的烷基化衍生物降低了肌肉乙酰胆碱酯酶对抑制的敏感性，而没有发挥其自身的抑制作用。
