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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Do alprazolam-induced changes in saccadic eye movement and psychomotor function follow the same time course?
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Do alprazolam-induced changes in saccadic eye movement and psychomotor function follow the same time course?

机译：阿普唑仑引起的眼跳运动和精神运动功能的变化是否遵循同一时间进程？

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摘要

The purpose of this study was to determine whether short-term tolerance develops to GABA-agonist-induced changes in saccadic eye movements (SEMs), and whether the time course for GABA-agonist induced onset and offset of impairment is similar for SEMs and for psychomotor function. An additional goal was to determine whether there are differences in sensitivity between SEMs and psychomotor function. Six healthy volunteers participated in this balanced double-blind, three-way crossover, single-dose study of placebo and two different dosage forms of the GABA-agonist alprazolam: a rapidly absorbed oral 1.5-mg compressed tablet (CT) and a 3.0-mg sustained release (SR) tablet. Treatments were separated by a 7-day washout period. Peak concentrations did not differ between CT and SR treatments, although area under the concentration-time curve (AUC) of alprazolam was greater after administration of SR than after CT, because plateau concentrations were attained after SR. Both SEM and psychomotor tests showed time-dependent responses consistent with the development of tolerance. SEMs discriminated the differences in rate of drug input of the CT and SR formulations, with impairment evident at low concentrations during absorption. SEM impairment also persisted longer than did psychomotor impairment. Peak saccade velocity is a more sensitive indicator of pharmacologic effects mediated by the GABA-benzodiazepine receptor complex than are psychomotor responses. This is probably the result of the very high GABA dependency of SEMs, along with their limited sensitivity to motivation.
机译：这项研究的目的是确定对GABA激动剂引起的眼跳运动（SEM）的短期耐受性是否发展，以及GABA激动剂引起的损伤发作和抵消的时程对于SEM和心理运动功能。另一个目标是确定SEM与精神运动功能之间的敏感性是否存在差异。六名健康志愿者参加了这项安慰剂和GABA激动剂阿普唑仑的两种不同剂型的平衡双盲，三向交叉，单剂量研究：快速吸收的口服1.5毫克压缩片剂（CT）和3.0毫克毫克缓释（SR）片剂。治疗间隔7天。尽管在SR给药后阿普唑仑的浓度-时间曲线（AUC）下的面积大于CT给药，但在CT和SR处理之间的峰值浓度没有差异，因为SR达到了高原浓度。 SEM和心理运动测试均显示出与时间相关的反应，与耐受性的发展一致。 SEM区分了CT和SR制剂的药物输入速率差异，在吸收过程中低浓度时明显受损。 SEM障碍的持续时间也比精神运动障碍的持续时间更长。与精神运动反应相比，峰值扫视速度是由GABA-苯并二氮杂receptor受体复合物介导的药理作用的更敏感指标。这可能是由于SEM对GABA的依赖性很高，以及它们对动力的敏感性有限所致。

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