van Helden H P, Van der Wiel H J, Wolthuis O L
Medical Biological Laboratory TNO, Rijswijk, The Netherlands.
J Pharm Pharmacol. 1988 Jan;40(1):35-41. doi: 10.1111/j.2042-7158.1988.tb05146.x.
Whether the temporary retention of intact soman in the rat and its subsequent delivery from tissues into the circulation of the blood is also demonstrable in guinea-pigs and marmosets has been investigated as was whether the soman simulator PDP (pinacolyl dimethylphosphinate) prevented this retention. Electric eel AChE, intravenously injected 1.5 h after an intravenous soman intoxication into anaesthetized, atropinized and artificially ventilated guinea-pigs (150 micrograms kg-1 soman), marmoset monkeys (100 micrograms kg-1 soman) and rats (330 and 172.5 micrograms kg-1 soman) lost its activity faster than enzyme injected in non-intoxicated animals. Electric eel AChE incubated in the presence of pectoralis or diaphragm muscle isolated from soman-intoxicated rats, guinea-pigs and marmosets 0.5 or 1.5 h after the intoxication, was progressively inhibited, indicating that those muscles still delivered soman into the incubation medium. In rats, PDP (6.4 mg kg-1 i.v.) pretreatment was effective in preventing inhibition of intravenously injected electric eel AChE 1.5 h after intoxication with a high dose of soman (330 micrograms kg-1). But after intoxication with a low dose (172.5 micrograms kg-1), PDP pretreatment was ineffective in this action, however, it did lead to less soman delivery from muscle tissue isolated 30 min following the 172.5 micrograms kg-1 soman intoxication, suggesting that there was less soman in the tissue. In PDP (6.4 mg kg-1 i.v.)-pretreated marmosets (100 micrograms kg-1 soman) and guinea-pigs (150 micrograms kg-1 soman), to the contrary, the trend was for the injected AChE to be more inhibited, whereas only slightly less soman was delivered from isolated muscle tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
已对豚鼠和狨猴体内是否也能证明大鼠体内存在梭曼的暂时留存及其随后从组织释放到血液循环中进行了研究,同时也研究了梭曼模拟物PDP(频哪基二甲基次膦酸酯)是否能阻止这种留存。在给麻醉、已用阿托品处理并进行人工通气的豚鼠(150微克/千克梭曼)、狨猴(100微克/千克梭曼)和大鼠(330微克/千克和172.5微克/千克梭曼)静脉注射梭曼中毒1.5小时后,静脉注射电鳗乙酰胆碱酯酶(150微克/千克),其活性丧失速度比在未中毒动物中注射的酶更快。在中毒0.5或1.5小时后,将电鳗乙酰胆碱酯酶与从梭曼中毒的大鼠、豚鼠和狨猴分离的胸肌或膈肌一起孵育,酶活性逐渐受到抑制,这表明这些肌肉仍在将梭曼释放到孵育介质中。在大鼠中,PDP(6.4毫克/千克静脉注射)预处理可有效防止在高剂量梭曼(330微克/千克)中毒1.5小时后静脉注射的电鳗乙酰胆碱酯酶受到抑制。但在低剂量(172.5微克/千克)中毒后,PDP预处理在此作用中无效,不过,它确实导致在172.5微克/千克梭曼中毒30分钟后分离的肌肉组织释放的梭曼减少,这表明组织中的梭曼较少。相反,在PDP(6.4毫克/千克静脉注射)预处理的狨猴(100微克/千克梭曼)和豚鼠(150微克/千克梭曼)中,注射的乙酰胆碱酯酶受抑制的趋势更明显,而从分离的肌肉组织释放的梭曼仅略有减少。(摘要截取自250字)