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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Time course of pharmacodynamic and pharmacokinetic effects of physostigmine assessed by functional brain imaging in humans.
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Time course of pharmacodynamic and pharmacokinetic effects of physostigmine assessed by functional brain imaging in humans.

机译：通过对人体进行功能性脑成像评估的毒扁豆碱的药效学和药代动力学作用的时程。

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In imaging studies of brain functions using pharmacological probes, identification of the time point at which central effects of intravenously infused drugs become stable is crucial to separate the effects of experimental variables from the concomitant changes in drug effects over time. We evaluated the time courses of the pharmacokinetics and pharmacodynamics, including butyrylcholinesterase inhibition and central neural responses, of physostigmine in healthy young subjects. Ten positron emission tomography (PET) scans that alternated between a rest condition (eyes open, ears unplugged) and a working memory for faces (WM) task were acquired in healthy subjects. Subjects in the drug group received a saline infusion for the first two scans, providing a baseline measure, then received an infusion of physostigmine for all subsequent scans. Subjects in the control group received a placebo infusion of saline for all scans. Physostigmine plasma levels and percent butyrylcholinesterase inhibition increased over time (p < 0. 0001), and both became stable by 40 min. Physostigmine decreased reaction time (RT) (p = 0.0005), and this effect was detected after 20 min of infusion and stable thereafter. Physostigmine also decreased regional cerebral blood flow (rCBF) in right prefrontal cortex during task (p = 0.0002), and this effect was detected after 40 min of infusion and stable thereafter. No change in RT or rCBF was observed in the control group. These results indicate that a 40-min infusion of physostigmine was necessary to obtain stable central effects. More generally, we have demonstrated that experimental effects can vary with time, especially during the initial phases of a drug infusion, indicating that it is critical that these changes are controlled.
机译：在使用药理学探针对脑功能进行影像学研究时，确定静脉输注药物的中心作用稳定的时间点对于区分实验变量的影响与药物作用随时间的变化是至关重要的。我们评估了健康年轻受试者中毒扁豆碱的药代动力学和药效学的时程，包括丁酰胆碱酯酶抑制和中枢神经反应。在健康受试者中，进行了十次正电子发射断层扫描（PET）扫描，这些扫描在休息状态（睁开眼睛，拔掉耳朵）和面部工作记忆（WM）任务之间交替进行。药物组中的受试者在前两次扫描中接受了盐水输注，提供了基线测量，然后在随后的所有扫描中接受了毒扁豆碱的注入。在所有扫描中，对照组的受试者均接受安慰剂的生理盐水注入。毒扁豆碱的血浆水平和丁酰胆碱酯酶抑制百分率随时间增加（p <0. 0001），并且都在40分钟后保持稳定。毒扁豆碱可缩短反应时间（RT）（p = 0.0005），并且在输注20分钟后即可检测到这种效果，此后稳定。毒扁豆碱在任务期间也降低了右前额叶皮层的局部脑血流量（rCBF）（p = 0.0002），并且在输注40分钟后检测到这种作用，此后稳定。对照组中未观察到RT或rCBF的变化。这些结果表明，为获得稳定的中枢作用，需要注入40分钟的毒扁豆碱。更普遍地说，我们已经证明实验效果会随时间变化，特别是在药物输注的初始阶段，这表明控制这些变化至关重要。

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