Blick D W, Murphy M R, Brown G C, Yochmowitz M G, Fanton J W, Hartgraves S L
Systems Research Laboratories, Division of Arvin/Calspan, United States Air Force, Armstrong Laboratory, Brooks AFB, Texas 78235-5000.
Toxicol Appl Pharmacol. 1994 Jun;126(2):311-8. doi: 10.1006/taap.1994.1121.
Effects of a peripherally active carbamate (pyridostigmine bromide) and a centrally active organophosphate (OP) nerve agent (soman) on performance by rhesus monkeys of a compensatory tracking (primate equilibrium platform, or PEP) task were measured using a balanced Latin-square design to determine the ED50 for pyridostigmine (0.66 mg/kg) and the up-and-down (titration) method to determine the ED50 for soman (2.50 micrograms/kg). We concluded that the PEP performance model is a sensitive and reliable indicator of anticholinesterase (anti-ChE) behavioral toxicity. We also found that soman, an irreversible inhibitor of acetylcholinesterase (AChE), is more than 100 times more behaviorally disruptive than the reversible peripheral inhibitor pyridostigmine, as indicated by the difference in ED50 doses expressed in molar terms. Soman's behavioral toxicity is severe at levels of serum cholinesterase inhibition (70-80%) at which pyridostigmine does not significantly affect performance. As a prophylactic treatment for OP agent poisoning, pyridostigmine has a substantial safety factor, since behavioral toxicity becomes significant only at approximately four times the proposed therapeutic dose.
采用平衡拉丁方设计，测定了外周活性氨基甲酸酯（溴吡斯的明）和中枢活性有机磷酸酯（OP）神经毒剂（梭曼）对恒河猴执行补偿性追踪任务（灵长类平衡平台，或PEP）的影响，以确定溴吡斯的明的半数有效剂量（ED50）为0.66毫克/千克，并用上下（滴定）法确定梭曼的ED50为2.50微克/千克。我们得出结论，PEP性能模型是抗胆碱酯酶（抗ChE）行为毒性的敏感且可靠指标。我们还发现，作为乙酰胆碱酯酶（AChE）的不可逆抑制剂，梭曼在行为上的干扰作用比可逆性外周抑制剂溴吡斯的明大100多倍，以摩尔表示的ED50剂量差异表明了这一点。在血清胆碱酯酶抑制水平（70 - 80%）时，梭曼的行为毒性严重，而此时溴吡斯的明对性能无显著影响。作为OP毒剂中毒的预防性治疗药物，溴吡斯的明具有很大的安全系数，因为只有在约为建议治疗剂量四倍时行为毒性才会显著。
