Anderson R J
Department of Pharmacology, George Washington University, Washington, D.C.
J Toxicol Environ Health. 1987;22(4):491-6. doi: 10.1080/15287398709531088.
A number of reports have documented the myopathy that accompanies exposure to irreversible acetylcholinesterase inhibitors. However, less information is available on the functional consequences of the myopathy. The purpose of this study was to examine the effects of diisopropylfluorophosphate (DFP) and soman on skeletal muscle contracture. Rats were given daily doses of DFP or soman, and the tetanic contracture of the triceps surae muscles was recorded at various exposure periods up to 20 d. DFP decreased tetanic contracture during 5-Hz stimulation. Increased stimulation up to 50 Hz did not enhance the effect. The muscles showed the greatest deficit on d 5. Continued dosing produced a slightly attenuated effect. Soman produced a frequency-dependent increase in muscle contracture. The increase was greatest on d 2 and 4, but remained elevated over the 20-d study. These results show that two drugs that presumably both raised levels of transmitter in the synaptic cleft as a result of esterase inhibition can produce either enhanced or decreased muscle contraction.
许多报告记录了接触不可逆乙酰胆碱酯酶抑制剂后伴随出现的肌病。然而,关于该肌病功能后果的信息较少。本研究的目的是检测二异丙基氟磷酸酯(DFP)和梭曼对骨骼肌挛缩的影响。给大鼠每日给予DFP或梭曼,并在长达20天的不同暴露时间段记录腓肠三头肌的强直挛缩情况。DFP在5Hz刺激期间可降低强直挛缩。将刺激频率提高到50Hz并不能增强这种效果。在第5天肌肉表现出最大的功能缺陷。持续给药产生的效果略有减弱。梭曼使肌肉挛缩呈频率依赖性增加。这种增加在第2天和第4天最大,但在整个20天的研究中一直保持在较高水平。这些结果表明,两种可能因酯酶抑制而使突触间隙递质水平升高的药物,可导致肌肉收缩增强或减弱。