Deshpande S S, Viana G B, Kauffman F C, Rickett D L, Albuquerque E X
Fundam Appl Toxicol. 1986 Apr;6(3):566-77.
The effectiveness of physostigmine and atropine pretreatment against the lethal effects of sarin was studied in rats given lethal subcutaneous injections (130 micrograms/kg) of the organophosphate. Pretreatment of these animals with physostigmine 30 min prior to injection of sarin reduced mortality to 28% and when the drug coadministered with atropine only 4% of the animals died. The latter treatment also reduced significantly the extent and duration of symptoms due to sarin; however, atropine, pyridostigmine, and neostigmine injected alone did not protect animals against the lethal effects of sarin. Physostigmine caused only slight inhibition of cholinesterase in blood and skeletal muscle. Cholinesterase activity in blood and muscle of rats pretreated with physostigmine before sarin administration was significantly higher than in tissues from rats injected with sarin alone. In rats receiving sarin following pretreatment with physostigmine, twitch potentiation of extensor muscles and maintenance of tension during tetanic stimulation of the nerve recovered to near control levels. Muscle function recovered despite significant inhibition of cholinesterase. Effective protection against lethality by physostigmine could be related to protection of cerebral cholinesterase since inhibition of this enzyme by sarin was lowered significantly after pretreatment with physostigmine. Alternatively, physostigmine may also interact with the nicotinic acetylcholine receptor ion-channel complex directly.
在给大鼠皮下注射致死剂量（130微克/千克）有机磷酸酯沙林的实验中，研究了毒扁豆碱和阿托品预处理对沙林致死效应的影响。在注射沙林前30分钟用毒扁豆碱预处理这些动物，可使死亡率降至28%；当该药物与阿托品联合使用时，只有4%的动物死亡。后一种处理方法还显著减轻了沙林所致症状的程度和持续时间；然而，单独注射阿托品、吡啶斯的明和新斯的明并不能保护动物免受沙林的致死效应。毒扁豆碱仅对血液和骨骼肌中的胆碱酯酶产生轻微抑制作用。在给予沙林之前用毒扁豆碱预处理的大鼠，其血液和肌肉中的胆碱酯酶活性显著高于单独注射沙林的大鼠组织中的活性。在用毒扁豆碱预处理后接受沙林注射的大鼠中，伸肌的抽搐增强以及在神经强直刺激期间的张力维持恢复到接近对照水平。尽管胆碱酯酶受到显著抑制，但肌肉功能仍得以恢复。毒扁豆碱对致死性的有效保护作用可能与对脑胆碱酯酶的保护有关，因为在用毒扁豆碱预处理后，沙林对该酶的抑制作用显著降低。或者，毒扁豆碱也可能直接与烟碱型乙酰胆碱受体离子通道复合物相互作用。
