Lagarde D, Milhaud C
Division de Neurophysiologie Appliquée, Centre d'Essais en Vol, Bretigny Sur Orge, France.
Sleep. 1990 Oct;13(5):441-8. doi: 10.1093/sleep/13.5.441.
An electroencephalographic (EEG) study on the rhesus monkey, primate model of human sleep, showed the significant wakening effect of a new psychostimulant, Modafinil. The first experiment, with single administration of three increasing doses of Modafinil (3, 6, and 12 mg/kg), was to determine the efficient threshold dose; the second experiment, with repeated administration of 22.5 mg/kg during 4 days, was to determine whether continuous wakefulness could be obtained without apparent behavioral disorders. Results of the first experiment showed a wakening effect above 6 mg/kg, but 12 mg/kg induced a sharp wakening effect with a significant decrease in all sleep stages. The second experiment induced important insomnia in all subjects for 4 days and 4 nights. No behavioral disorder was observed. Modafinil has a wakening effect at the dose of 6 mg/kg in rhesus monkeys and induces quasicontinuous wakefulness for 4 total days and nights with daily administration of 22.5 mg/kg, with no behavioral disorders. Modafinil should therefore find interesting applications in sleep disorder treatments.
一项针对恒河猴(人类睡眠的灵长类动物模型)的脑电图(EEG)研究表明,新型精神振奋药莫达非尼具有显著的唤醒作用。第一个实验是单次给予三种递增剂量的莫达非尼(3、6和12毫克/千克),以确定有效阈剂量;第二个实验是在4天内重复给予22.5毫克/千克,以确定是否能在无明显行为障碍的情况下实现持续清醒。第一个实验的结果显示,剂量高于6毫克/千克时有唤醒作用,但12毫克/千克会引发明显的唤醒作用,且所有睡眠阶段均显著减少。第二个实验使所有受试者在4天4夜中出现严重失眠。未观察到行为障碍。莫达非尼在恒河猴中剂量为6毫克/千克时具有唤醒作用,每日给予22.5毫克/千克可使其在4个整日整夜中实现近似持续的清醒,且无行为障碍。因此,莫达非尼在睡眠障碍治疗中应会有有趣的应用。