Diaz-Alejo N, Pellin M C, Vicedo J L, Vilanova E
Departamento de Neuroquimica, Facultad de Medicina, Universidad de Alicante, Spain.
Neurotoxicol Teratol. 1990 Nov-Dec;12(6):615-7. doi: 10.1016/0892-0362(90)90072-k.
The in vitro and in vivo biochemical properties of O-hexyl, O-dichlorophenyl phosphoramidate (hexyl-DCP) as inhibitor of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) were studied, as well as their neurotoxic effects. The differences found were suggested to be due to biotransformation effects. In this work, the in vitro time-dependent degradation of hexyl-DCP by plasma, liver and brain homogenates of rat and hen at 37 degrees C at pH 7.4 are studied using 100 nM initial concentration. The loss of inhibitory potency against AChE was used as sensor of the biodegradation rate. An approximate estimation of the residual compound was made by comparison with an inhibition calibration curve. The rate of enzymatic degradation was corrected for the spontaneous hydrolysis. Rat tissues showed some higher activities (24, 17, 1 mU/g for plasma, liver, and brain, respectively) than hen (17, 6, 1 mU/g), with activities being highest for plasma and lowest for brain. Hexyl-DCP is a chiral compound. The loss of anti-AChE power could be due to degradation of only one of the two stereoisomers.
研究了O-己基-O-二氯苯基磷酰胺酯(己基-DCP)作为乙酰胆碱酯酶(AChE)和神经病变靶酯酶(NTE)抑制剂的体外和体内生化特性,以及它们的神经毒性作用。发现的差异被认为是由于生物转化作用。在这项工作中,使用100 nM的初始浓度,研究了大鼠和母鸡的血浆、肝脏和脑匀浆在37℃、pH 7.4条件下对己基-DCP的体外时间依赖性降解。以对AChE抑制效力的丧失作为生物降解速率的指标。通过与抑制校准曲线比较对残留化合物进行了近似估算。对酶促降解速率进行了自发水解校正。大鼠组织(血浆、肝脏和脑的活性分别为24、17、1 mU/g)显示出比母鸡组织(17、6、1 mU/g)更高的活性,其中血浆活性最高,脑活性最低。己基-DCP是一种手性化合物。抗AChE能力的丧失可能仅归因于两种立体异构体之一的降解。