Smith A P
Chemical and Biological Defense Establishment, Salisbury, Wiltshire, UK.
J Pharm Pharmacol. 1993 Mar;45(3):176-81. doi: 10.1111/j.2042-7158.1993.tb05528.x.
In-vivo administration of the irreversible anticholinesterases sarin and soman has been shown to produce long-term effects on latency and variability of latency of muscle action potentials in in-vitro mouse diaphragm muscle preparations. The maximum observed effects occurred three days post-soman administration and seven days post-sarin administration, and were no longer detectable 28 days later. With both anticholinesterases the increase in latency, and variability of latency, was reduced by pyridostigmine pretreatment. Therapeutic administration of pralidoxime mesylate effectively prevented the sarin-induced effects when given after a delay of 24 h. In contrast, the effectiveness of pralidoxime mesylate declined rapidly when its administration was delayed following soman. These findings are consistent with this action of soman and sarin being a product of acetylcholinesterase inhibition. The results obtained with sarin suggest that a period of acetylcholinesterase inhibition in excess of 24 h is required to trigger the events leading to the production of this long-term effect.
已证明,对小鼠膈肌体外制备物进行体内给予不可逆抗胆碱酯酶剂沙林和梭曼,会对肌肉动作电位的潜伏期和潜伏期变异性产生长期影响。观察到的最大效应出现在给予梭曼后三天和给予沙林后七天,28天后不再可检测到。使用这两种抗胆碱酯酶剂时,给予吡啶斯的明预处理可减少潜伏期的增加和潜伏期变异性。在延迟24小时后给予甲磺酸解磷定进行治疗性给药可有效预防沙林诱导的效应。相比之下,在给予梭曼后延迟给药时,甲磺酸解磷定的有效性迅速下降。这些发现与梭曼和沙林的这种作用是乙酰胆碱酯酶抑制产物一致。用沙林获得的结果表明,需要超过24小时的乙酰胆碱酯酶抑制期才能触发导致产生这种长期效应的事件。