Buccafusco J J, Smith M D
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912.
Res Commun Chem Pathol Pharmacol. 1990 Feb;67(2):219-27.
The antitumor agent caracemide [N-acetyl-N-(methylcarbamoyloxy)-N'-methylurea] has been observed to induce signs of cholinergic activation in both animal and human studies at high clinical and toxic levels. The present study was designed to further characterize the ability of caracemide to inhibit cholinesterase both in vivo and in vitro. Caracemide produced a time-dependent inhibition of purified acetylcholinesterase, pseudocholinesterase and rat brain homogenate cholinesterase with IC50 values of 0.60, 0.55 and 17.8 microM, respectively, at the maximal time point of inhibition. Analysis of Lineweaver-Burke plots derived from inhibition of brain homogenates revealed predominantly competitive type inhibition at both initial and maximal incubation times. Intravenous administration of caracemide to rats resulted in a dose-dependent inhibition of brain cholinesterase activity, with the greatest inhibition occurring in the cortex.
抗肿瘤药物卡醋胺[N-乙酰基-N-(甲基氨甲酰氧基)-N'-甲基脲]在动物和人体研究中均观察到，在高临床剂量和中毒剂量水平时会引发胆碱能激活迹象。本研究旨在进一步表征卡醋胺在体内和体外抑制胆碱酯酶的能力。卡醋胺对纯化的乙酰胆碱酯酶、假性胆碱酯酶和大鼠脑匀浆胆碱酯酶产生时间依赖性抑制，在抑制的最大时间点，其IC50值分别为0.60、0.55和17.8微摩尔。对源自脑匀浆抑制的Lineweaver-Burke图分析显示，在初始和最大孵育时间均主要为竞争性抑制类型。给大鼠静脉注射卡醋胺导致脑胆碱酯酶活性呈剂量依赖性抑制，其中皮质的抑制作用最强。
