Kelly T H, Foltin R W, Serpick E, Fischman M W
Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington 40536-0086, USA.
Behav Pharmacol. 1997 Feb;8(1):47-57.
The purpose of this study was to examine, in healthy volunteers without histories of extensive sedative use, the acute behavioral effects of doses of alprazolam used in clinical applications. Subjects participated in daily sessions over 12 study days. They consumed a standard breakfast, received an oral drug dose (0, 0.25, 0.5, 1 mg) and completed performance tasks for 3 hours after dosing. Tasks included a digit-symbol substitution task, a repeated-acquisition of response sequences task, a differential reinforcement of low response rate task designed to monitor time estimation, a number recognition task, and a second-order repeated-acquisition of response sequences task. Each active dose was administered prior to two sessions, according to a randomized block design, and placebo sessions separated successive active-dose sessions. With the exception of the second-order repeated acquisition of response sequences task, dose-related changes in performance were observed during all tasks, but effects were significant only following the 1 mg dose. No drug-related changes were observed on visual-analog scale ratings of drug effect. The data indicate that the risk of adverse performance effects following use of alprazolam is related to dose, with risks increasing at doses at or above 0.5 mg.
本研究的目的是在无长期使用镇静剂病史的健康志愿者中，考察临床应用剂量的阿普唑仑的急性行为效应。受试者在12个研究日中每天参加实验环节。他们食用标准早餐，接受口服药物剂量（0、0.25、0.5、1毫克），并在给药后3小时内完成行为任务。任务包括数字符号替换任务、反应序列重复习得任务、旨在监测时间估计的低反应率差异强化任务、数字识别任务以及二阶反应序列重复习得任务。根据随机区组设计，在两个实验环节前给予每个有效剂量，且安慰剂实验环节分隔连续的有效剂量实验环节。除二阶反应序列重复习得任务外，在所有任务中均观察到与剂量相关的行为表现变化，但仅在1毫克剂量后效应显著。在药物效应的视觉模拟量表评分上未观察到与药物相关的变化。数据表明，使用阿普唑仑后出现不良行为效应的风险与剂量相关，在0.5毫克及以上剂量时风险增加。
