Roy-Byrne P P, Cowley D S, Radant A, Hommer D, Greenblatt D J
Department of Psychiatry and Behavioral Sciences, University of Washington Medical School, Seattle 98104.
Psychopharmacology (Berl). 1993;110(1-2):85-91. doi: 10.1007/BF02246954.
The utility of several measures of saccadic and smooth pursuit eye movements as benzodiazepine pharmacodynamic measures was explored in 24 psychiatrically and medically health control subjects. Measures of sedation and memory impairment were also included. Subjects received four logarithmically increasing doses of intravenous diazepam at 15-min intervals on 1 day resulting in monotonically increasing plasma diazepam levels, and placebo on another day in random order 1 week apart. Measures were collected twice at baseline, once after each dose of diazepam/placebo and twice more, 15 and 30 min after the last dose. Peak saccadic velocity and smooth pursuit gain showed the greatest overall and dose-dependent drug effect among eye movement measures. Although effect sizes at the highest dose for memory impairment and self-rated sedation were comparable to these two measures, reliability (i.e., placebo-day fluctuation) with these measures was considerably poorer. Log-linear pharmacodynamic modeling was used to calculate the effective dose (ED30) or concentration (EC30) required to reduce saccadic velocity or pursuit gain by 30%. Almost all (23/24) subjects had linear and easily interpretable plots for saccadic velocity, while a majority (19/24) of subjects had interpretable plots for smooth pursuit gain. The distribution of ED30 and EC30 values showed a wide range of sensitivities to diazepam. These findings suggest that saccadic velocity and smooth pursuit gain are sensitive, reliable, quantitative benzodiazepine pharmacodynamic measures.
在24名精神和医学健康对照受试者中，探讨了几种眼跳和平稳跟踪眼球运动测量指标作为苯二氮䓬类药物药效学测量指标的效用。还纳入了镇静和记忆损害的测量指标。受试者在1天内每隔15分钟静脉注射四次对数递增剂量的地西泮，导致血浆地西泮水平单调增加，在1周后随机顺序的另一天注射安慰剂。在基线时收集两次测量指标，在每次注射地西泮/安慰剂后收集一次，在最后一次注射后15分钟和30分钟再收集两次。在眼球运动测量指标中，眼跳峰值速度和平稳跟踪增益显示出最大的总体和剂量依赖性药物效应。尽管最高剂量时记忆损害和自评镇静的效应大小与这两项测量指标相当，但这些测量指标的可靠性（即安慰剂日波动）要差得多。使用对数线性药效学模型计算将眼跳速度或跟踪增益降低30%所需的有效剂量（ED30）或浓度（EC30）。几乎所有（23/24）受试者的眼跳速度图呈线性且易于解释，而大多数（19/24）受试者的平稳跟踪增益图可解释。ED30和EC30值的分布显示出对地西泮的广泛敏感性。这些发现表明，眼跳速度和平稳跟踪增益是敏感、可靠的定量苯二氮䓬类药物药效学测量指标。
