Saletu B, Frey R, Krupka M, Anderer P, Grünberger J, Barbanoj M J
Department of Psychiatry, University of Vienna, Austria.
Int J Clin Pharmacol Res. 1989;9(3):183-95.
Modafinil (CRL 40476) is a recently developed central alpha adrenergic agonist with vigilance-promoting properties. In a double-blind, placebo-controlled sleep laboratory study, its single-dose effects on objectively and subjectively evaluated sleep, morning awakening, and early morning behaviour were investigated and compared with amphetamine. Ten young healthy volunteers of both sexes spent 12 nights in the sleep laboratory: one adaptation night, one baseline night, five drug nights (100 mg and 200 mg modafinil; 10 mg and 20 mg d-amphetamine; placebo) and five subsequent washout nights. The drugs were administered in one week intervals according to a Latin square design. Somnopolygraphic investigations were performed between 22h30 and 06h00. Subjects received the drug orally half an hour before bedtime. A self-rating scale for sleep and awakening quality and early morning behavior was completed subsequent to the morning toilet. Thereafter, noopsychic and thymopsychic variables were evaluated utilizing a psychometric test-battery. Statistical analyses of objective sleep variables demonstrated that modafinil causes no significant changes as compared to a placebo. Sleep initiation remained unchanged after all of the drugs, while sleep maintenance was impaired dose-dependently after d-amphetamine. Thus, total sleep time and sleep efficiency decreased significantly after 20 mg d-amphetamine as compared to the placebo and modafinil. In regard to sleep architecture a reduction of sleep stage 2 and rapid eye movement-sleep occurred under d-amphetamine while modafinil did not exhibit such an effect. Subjective sleep quality was significantly better after modafinil than after the reference compound. Subjective awakening quality and well-being in the morning did not show any significant findings. Furthermore, no differences were observed between the placebo and the other drugs concerning objective awakening quality (evaluated by psychometric tests). Critical flicker frequency increased significantly after 20 mg d-amphetamine as compared to the placebo. Pulse rate and evening and morning blood pressure remained unchanged. These data stress the necessity to differentiate between "vigility-increasing" properties of amphetamine and "vigilance-promoting" properties of modafinil.
莫达非尼（CRL 40476）是一种最近研发的具有促进警觉特性的中枢α肾上腺素能激动剂。在一项双盲、安慰剂对照的睡眠实验室研究中，研究了其单剂量对客观和主观评估的睡眠、早晨觉醒及清晨行为的影响，并与苯丙胺进行了比较。10名年轻健康的男女志愿者在睡眠实验室度过了12个夜晚：一个适应夜、一个基线夜、五个用药夜（100毫克和200毫克莫达非尼；10毫克和20毫克右旋苯丙胺；安慰剂）以及随后的五个洗脱夜。药物按照拉丁方设计每隔一周给药一次。在22:30至06:00之间进行多导睡眠图检查。受试者在就寝前半小时口服药物。早晨洗漱后完成一份关于睡眠和觉醒质量以及清晨行为的自评量表。此后，利用一套心理测量测试评估精神和情绪变量。对客观睡眠变量的统计分析表明，与安慰剂相比，莫达非尼未引起显著变化。所有药物给药后入睡情况均未改变，而右旋苯丙胺给药后睡眠维持情况出现剂量依赖性受损。因此，与安慰剂和莫达非尼相比，20毫克右旋苯丙胺给药后总睡眠时间和睡眠效率显著降低。关于睡眠结构，右旋苯丙胺给药后睡眠第二阶段和快速眼动睡眠减少，而莫达非尼未表现出这种效应。莫达非尼给药后的主观睡眠质量显著优于参比化合物给药后。早晨的主观觉醒质量和幸福感未显示任何显著差异。此外，在客观觉醒质量方面（通过心理测量测试评估），安慰剂与其他药物之间未观察到差异。与安慰剂相比，20毫克右旋苯丙胺给药后临界闪烁频率显著增加。脉搏率以及傍晚和早晨血压保持不变。这些数据强调了区分苯丙胺的“提高警觉性”特性和莫达非尼的“促进警觉”特性的必要性。
