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非苯二氮䓬类镇静催眠药扎来普隆在大鼠中的脑电图特性

Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats.

作者信息

Noguchi Hideaki, Kitazumi Kazuhiro, Mori Megumi, Shiba Toshiharu

机构信息

Medical Research Laboratories, Wyeth Lederle (Japan), Ltd, Saitama, Japan.

出版信息

J Pharmacol Sci. 2004 Mar;94(3):246-51. doi: 10.1254/jphs.94.246.

Abstract

The encephalographic (EEG) properties of zaleplon were investigated in comparison with those of other sedative hypnotics in conscious rats with chronically implanted electrodes. The oral administration of zaleplon (0.25-1.0 mg/kg), triazolam (0.0625-0.25 mg/kg), zopiclone (1.0-4.0 mg/kg), brotizolam (0.0625-0.25 mg/kg), and nitrazepam (0.125-0.5 mg/kg) lengthened the total sleep in a dose-dependent manner. On distribution of sleep-wakefulness stages, zaleplon, in particular, increased the slow wave deep sleep (SWDS), whereas triazolam, brotizolam, and nitrazepam increased the slow wave light sleep (SWLS) in a dose-dependent manner. Zopiclone significantly increased the SWDS at a dose of 2 mg/kg and both the SWLS and the SWDS at a dose of 4 mg/kg. All tested hypnotics caused no influence on fast wave sleep (FWS) at doses tested. The appearance of the sleep-inducing activity of zaleplon was more rapid than those of any compounds tested, and zaleplon significantly increased the relative EEG power density in the delta frequency band over that of triazolam at 20 and 30 min after the administration in the spectral analysis. Therefore, the present findings suggest that the non-benzodiazepine zaleplon can be expected to exhibit high practical potential as a hypnotic and is characterized by an increase in SWDS with rapid onset of hypnotic action.

摘要

在长期植入电极的清醒大鼠中,将扎来普隆的脑电图(EEG)特性与其他镇静催眠药进行了比较研究。口服扎来普隆(0.25 - 1.0毫克/千克)、三唑仑(0.0625 - 0.25毫克/千克)、佐匹克隆(1.0 - 4.0毫克/千克)、溴替唑仑(0.0625 - 0.25毫克/千克)和硝西泮(0.125 - 0.5毫克/千克)可使总睡眠时间呈剂量依赖性延长。在睡眠 - 觉醒阶段分布方面,扎来普隆尤其增加了慢波深度睡眠(SWDS),而三唑仑、溴替唑仑和硝西泮则以剂量依赖性方式增加了慢波浅睡眠(SWLS)。佐匹克隆在2毫克/千克剂量时显著增加了SWDS,在4毫克/千克剂量时同时增加了SWLS和SWDS。所有测试的催眠药在测试剂量下对快波睡眠(FWS)均无影响。扎来普隆诱导睡眠活性的出现比任何测试化合物都更快,并且在频谱分析中,给药后20和30分钟时,扎来普隆使δ频段的相对脑电图功率密度比三唑仑显著增加。因此,目前的研究结果表明,非苯二氮䓬类药物扎来普隆有望作为一种催眠药展现出较高的实际应用潜力,其特点是增加SWDS且催眠作用起效迅速。

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