Romano J A, Terry M R, Murrow M L, Mays M Z
U.S. Army Medical Research Institute of Chemical Defense, Drug Assessment Division, Aberdeen Proving Ground, MD 21010-5425.
Drug Chem Toxicol. 1991;14(1-2):21-44. doi: 10.3109/01480549109017867.
The lethal and incapacitating effects of the toxic organophosphorus (OP) agent, soman were evaluated in guinea pigs. The protective effects of the standard therapies atropine sulfate (ATR) and pralidoxime chloride (2-PAM) in minimizing or reducing soman-produced lethality and incapacitation (evaluated using a modification of the rat conditioned avoidance procedure) were also studied. At 0.75 and 1.5 LD50 soman was extremely toxic and fast-acting; its effects appeared within five minutes, and its lethal effects occurred within the first three hours. Therapeutic combinations of ATR (64 or 128 mg/kg) and 2-PAM (25 or 100 mg/kg) protected animals from the lethality of soman, but not from its incapacitating effects. However, therapeutic treatment with ATR and 2-PAM also produced a behavioral toxicity in its own right, an effect which lasted for at least three hours in the guinea pig. This behavioral toxicity was lessened by reducing ATR dosage from 128 to 64 mg/kg, but 2-PAM dosage did not influence the behavioral toxicity of the treatment combinations within the range of dosages studied.
在豚鼠身上评估了有毒有机磷（OP）制剂梭曼的致死和致残作用。还研究了标准疗法硫酸阿托品（ATR）和氯解磷定（2-PAM）在最小化或降低梭曼所致致死率和致残率方面的保护作用（使用对大鼠条件性回避程序的改良方法进行评估）。在0.75和1.5倍半数致死剂量（LD50）时，梭曼具有极高毒性且起效迅速；其作用在五分钟内显现，致死作用在前三个小时内发生。ATR（64或128毫克/千克）和2-PAM（25或100毫克/千克）的治疗组合可保护动物免受梭曼致死作用的影响，但不能防止其致残作用。然而，ATR和2-PAM的治疗本身也会产生行为毒性，这种作用在豚鼠中至少持续三个小时。将ATR剂量从128毫克/千克降至64毫克/千克可减轻这种行为毒性，但在所研究的剂量范围内，2-PAM剂量并未影响治疗组合的行为毒性。
