Slattum P W, Venitz J, Barr W H
Department of Pharmacy and Pharmaceutics, Virginia Commonwealth University, Richmond 23298-0533, USA.
J Clin Pharmacol. 1996 Nov;36(11):1039-50. doi: 10.1177/009127009603601108.
The objective of this investigation was to evaluate a series of potential pharmacodynamic measures of central nervous system stimulation, including quantitative electroencephalography (EEG) and neuroendocrine, mood, and psychomotor performance measures. The reproducibility and sensitivity of the measures were compared. The study was conducted in two parts. The first part investigated the interindividual and intraindividual variability associated with a series of potential pharmacologic response measures under baseline (i.e., drug-free) conditions. It was an open-label, three-period pilot study in which healthy male volunteers underwent a series of tests (EEG, a visual continuous performance task, a finger tapping task, and self-rated mood scales) repeatedly during each study period. The second part evaluated the sensitivity of a series of potential response measures to detect the effects of dextroamphetamine, and was a double-blind, placebo-controlled, four-period crossover study in nine healthy male volunteers. Subjects received 5 mg, 10 mg, or 20 mg of dextroamphetamine or placebo orally and underwent the same series of tests as in Part I in addition to blood collection for determination of serum prolactin and dextroamphetamine levels. Peripheral response to dextroamphetamine was assessed by heart rate and blood pressure measurement. The greatest variability among days, within days, and among participants was associated with the quantitative electroencephalographic parameters studied. First-session effects were apparent for several of the tests, including EEG. Consistent response on EEG (increased alpha power) to dextroamphetamine was observed only in the three subjects who had a baseline alpha activity greater than 35%. Serum prolactin levels were inversely associated with the amount of dextroamphetamine administered, with the largest decrease in serum prolactin levels observed after the 5-mg dose, and this finding was statistically significant. Mood scales showed that three of nine participants experienced dysphoria after at least one dose level of dextroamphetamine. The effect on mood was generally greater as the dose increased. Doses could not be distinguished based on the results of the performance tests. Serum prolactin concentration was the most sensitive measure of central nervous system stimulation on EEG produced by dextroamphetamine under these study conditions. Cardiovascular measures were more sensitive measures of dextroamphetamine effects than the central nervous system measures.
本研究的目的是评估一系列中枢神经系统刺激的潜在药效学指标，包括定量脑电图（EEG）以及神经内分泌、情绪和精神运动表现指标。对这些指标的可重复性和敏感性进行了比较。该研究分两部分进行。第一部分研究了在基线（即无药物）条件下，一系列潜在药理反应指标所涉及的个体间和个体内变异性。这是一项开放标签的三期试点研究，健康男性志愿者在每个研究期间重复接受一系列测试（EEG、视觉持续操作任务、手指敲击任务和自评情绪量表）。第二部分评估了一系列潜在反应指标检测右旋苯丙胺效应的敏感性，这是一项在九名健康男性志愿者中进行的双盲、安慰剂对照、四期交叉研究。受试者口服5毫克、10毫克或20毫克右旋苯丙胺或安慰剂，并除了采集血液以测定血清催乳素和右旋苯丙胺水平外，还接受了与第一部分相同的一系列测试。通过测量心率和血压评估对右旋苯丙胺的外周反应。在研究的天数之间、一天内以及参与者之间，最大的变异性与所研究的定量脑电图参数相关。包括EEG在内的几项测试在首次测试时就有明显效果。仅在三名基线α波活动大于35%的受试者中观察到EEG对右旋苯丙胺有一致反应（α波功率增加）。血清催乳素水平与右旋苯丙胺给药量呈负相关，在5毫克剂量后观察到血清催乳素水平下降幅度最大，且这一发现具有统计学意义。情绪量表显示，九名参与者中有三名在至少一个剂量水平的右旋苯丙胺后出现烦躁不安。随着剂量增加，对情绪的影响通常更大。根据操作测试结果无法区分不同剂量。在这些研究条件下，血清催乳素浓度是右旋苯丙胺对EEG产生中枢神经系统刺激的最敏感指标。心血管指标比中枢神经系统指标更能敏感地反映右旋苯丙胺的作用。
