Carmona G N, Baum I, Schindler C W, Goldberg S R, Jufer R, Cone E, Slaughter E, Belendiuk G W, Gorelick D A
Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Life Sci. 1996;59(11):939-43. doi: 10.1016/0024-3205(96)00392-x.
In vitro studies have implicated butyrylcholinesterase (BChE, E.C.3.1.1.8) as the major enzyme for metabolizing cocaine in humans, but little is known about endogenous BChE activity in monkeys and other animals often used in preclinical studies of cocaine. We compared BChE activity in 18 rhesus and 11 squirrel monkeys, using the colorimetric method of Ellman with butyrylthiocholine as substrate, and in vitro cocaine half-life in pooled plasma samples measuring cocaine concentrations over 60 minutes by GC-MS. Rhesus monkeys had a significantly higher plasma BChE activity than squirrel monkeys (8.2 +/- 0.5 U/L vs. 2.8 +/- 0.5 U/L), and a three-fold shorter in vitro cocaine half-life (20.1 min vs. 60.2 min). BChE activity in rhesus monkeys was comparable to the activity reported in humans. There was no significant influence of age, weight, or prior cocaine exposure. These results indicate that BChE level can vary between species of non-human primates, a factor that should be taken into account when studying drugs such as cocaine which are metabolized by BChE.
体外研究表明，丁酰胆碱酯酶（BChE，E.C.3.1.1.8）是人体内代谢可卡因的主要酶，但对于在可卡因临床前研究中常用的猴子和其他动物体内的内源性BChE活性，人们了解甚少。我们采用以丁酰硫代胆碱为底物的埃尔曼比色法，比较了18只恒河猴和11只松鼠猴的BChE活性，并通过气相色谱-质谱联用仪（GC-MS）测量合并血浆样本中60分钟内的可卡因浓度，以此测定体外可卡因半衰期。恒河猴的血浆BChE活性显著高于松鼠猴（8.2±0.5 U/L对2.8±0.5 U/L），且体外可卡因半衰期短三倍（20.1分钟对60.2分钟）。恒河猴的BChE活性与人类报告的活性相当。年龄、体重或既往可卡因暴露对此并无显著影响。这些结果表明，非人类灵长类动物不同物种之间的BChE水平可能存在差异，在研究诸如可卡因这类由BChE代谢的药物时，这一因素应予以考虑。
