Videbaek C, Friberg L, Holm S, Wammen S, Foged C, Andersen J V, Dalgaard L, Lassen N A
Department of Neurology, University Hospital, Rigshospitalet, Copenhagen, Denmark.
Eur J Pharmacol. 1993 Nov 2;249(1):43-51. doi: 10.1016/0014-2999(93)90660-a.
This study is based on the steady state method for the calculation of Kd values recently described by Lassen (J. Cereb. Blood Flow Metab. 12 (1992), 709), in which a constant infusion of the examined nonradioactive ligand is used with a bolus injection of tracer. Eight volunteers were examined twice, once without receptor blockade and once with a constant degree of partial blockade of the benzodiazepine receptors by infusion of nonradioactive flumazenil (Lanexat) or midazolam (Dormicum). Single photon emission computer tomography and blood sampling were performed intermittently for 6 h after bolus injection of [123I]iomazenil. The tracer in plasma was determined by high-pressure liquid chromatography and also by a simple octanol extraction procedure. The free concentration of flumazenil and midazolam in plasma water averaged 52% and 3.5% of that in whole plasma. The Kd values for the entire cortical rim for flumazenil were 7.4, 10.0, 10.3 and 17.7 nmol/l plasma water and, for midazolam, 73, 76, 58 and 30 nmol/l plasma water. The variation exceeds random methodological error and is probably due to interindividual differences in receptor affinity. The Kd level of midazolam is considerably higher than expected from the results of in vitro studies.
本研究基于拉森（《脑血流与代谢杂志》12(1992)，709）最近描述的用于计算解离常数（Kd）值的稳态方法，该方法中使用恒定输注被检测的非放射性配体并推注示踪剂。8名志愿者接受了两次检查，一次无受体阻断，一次通过输注非放射性氟马西尼（兰美抒）或咪达唑仑（多美康）对苯二氮䓬受体进行恒定程度的部分阻断。在推注[123I]碘美普尔后间歇性地进行单光子发射计算机断层扫描和采血，持续6小时。血浆中的示踪剂通过高压液相色谱法以及一种简单的辛醇萃取程序进行测定。血浆水中氟马西尼和咪达唑仑的游离浓度平均分别为全血浆中浓度的52%和3.5%。氟马西尼在整个皮质边缘的Kd值为血浆水7.4、10.0、10.3和17.7nmol/L，咪达唑仑的Kd值为血浆水73、76、58和30nmol/L。这种变化超过了随机方法误差，可能是由于受体亲和力的个体差异所致。咪达唑仑的Kd水平远高于体外研究结果的预期。
