ACUTE BEHAVIORAL TOXICITY OF PYRIDOSTIGMINE OR SOMAN IN PRIMATES
ACUTE BEHAVIORAL TOXICITY OF PYRIDOSTIGMINE OR SOMAN IN PRIMATES
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DOI：
10.1006/taap.1994.1121
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发表时间：
1994-06-01
影响因子：
3.8
通讯作者：
HARTGRAVES, SL
中科院分区：
文献类型：
--
作者：
BLICK, DW;MURPHY, MR;HARTGRAVES, SL
外周活性氨基甲酸酯的作用（溴化吡啶斯的明）和中枢活性有机磷（OP）神经毒剂（梭曼）对恒河猴代偿性追踪行为的影响（灵长类动物平衡平台，或PEP）任务，以确定吡啶斯的明的ED 50（0.66 mg/kg）和升降（滴定）法测定梭曼的ED 50（2.50 μ g/kg）。我们的结论是PEP性能模型是一个敏感和可靠的指标抗胆碱酯酶（抗胆碱酯酶）的行为毒性。我们还发现，梭曼，一种不可逆的乙酰胆碱酯酶（AChE）抑制剂，是超过100倍以上的行为破坏比可逆的外周抑制剂吡啶斯的明，在ED 50剂量的差异表示的摩尔。梭曼的行为毒性在血清胆碱酯酶抑制水平（70-80%）下是严重的，在此水平下吡啶斯的明不会显著影响表现。作为OP药物中毒的预防性治疗，吡啶斯的明具有相当大的安全系数，因为行为毒性仅在约四倍于拟定治疗剂量时才变得显著。(C)1994年出版社出版。
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 mu g/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. (C) 1994 Academic Press, Inc.