Ueki S, Watanabe S, Yamamoto T, Kataoka Y, Tazoe N, Shibata S, Shibata K, Ohta H, Kawahara K, Takano M, Suwandi D, Lee S C, Liou S Y
Nihon Yakurigaku Zasshi. 1981 May;77(5):483-509.
The behavioral and electroencephalographic effects of alprazolam and its metabolites were investigated in mice, rats and rabbits, and compared with the data on diazepam, lorazepam and nitrazepam. Locomotor activity of mice in an open-field situation was increased with smaller doses of alprazolam and nitrazepam but not with diazepam and lorazepam. Alprazolam increased the hyperactivity induced by methamphetamine in mice. The anticonflict effects of alprazolam in rats were more potent than those of diazepam and lorazepam. In suppressing hyperemotionality and muricide of olfactory bulbectomized rats, alprazolam was more potent than diazepam and fairly equal to that of lorazepam. Muricide of raphe-lesioned rats was markedly inhibited by alprazolam. Mescaline-induced head-twitches in mice were more markedly increased with alprazolam than with nitrazepam and diazepam. Alprazolam, diazepam and lorazepam prevented both maximal electroshock and pentetrazol convulsions in mice. Alprazolam was more potent than diazepam and lorazepam in potentiating thiopental, ether and ethanol anesthesia in mice. In the impaired rotarod performance, alprazolam was more potent than diazepam and lorazepam in mice, but was much less potent than diazepam and lorazepam in mice, but was much less potent than lorazepam in rats. In conscious rabbits with chronically implanted electrodes, alprazolam induced a drowsy EEG pattern and depressed the EEG arousal response not only to auditory stimulation but also to mesencephalic reticular stimulation. The EEG effect of alprazolam was approx. twice that of diazepam. The pharmacological activity of alpha-hydroxyalprazolam was approx. one third that of alprazolam. However, 5-chloro-2-(3-hydromethyl-5-methyl-4H-1, 2,4-triazolo-4-yl) benzophenone showed no pharmacological activity. These results indicate that alprazolam possesses pharmacologic properties characteristic to benzodiazepines and that the activity is more potent than diazepam. In addition, alprazolam seems to have a specific effect on the central serotonergic mechanisms.
在小鼠、大鼠和兔子身上研究了阿普唑仑及其代谢产物的行为和脑电图效应，并与地西泮、劳拉西泮和硝西泮的数据进行了比较。在旷场环境中，较小剂量的阿普唑仑和硝西泮可增加小鼠的自发活动，但地西泮和劳拉西泮则无此作用。阿普唑仑可增强甲基苯丙胺诱导的小鼠多动。阿普唑仑对大鼠的抗冲突作用比地西泮和劳拉西泮更强。在抑制嗅球切除大鼠的过度情绪化和杀鼠行为方面，阿普唑仑比地西泮更强，与劳拉西泮相当。阿普唑仑可显著抑制中缝核损伤大鼠的杀鼠行为。与硝西泮和地西泮相比，阿普唑仑更显著地增强了小鼠中由三甲氧苯乙胺诱导的头部抽搐。阿普唑仑、地西泮和劳拉西泮均可预防小鼠的最大电休克和戊四氮惊厥。在增强小鼠硫喷妥钠、乙醚和乙醇麻醉方面，阿普唑仑比地西泮和劳拉西泮更强。在小鼠转棒试验能力受损的情况下，阿普唑仑比地西泮和劳拉西泮更强，但在大鼠中比劳拉西泮弱得多。在长期植入电极的清醒兔子中，阿普唑仑可诱导出困倦的脑电图模式，并不仅抑制对听觉刺激的脑电图觉醒反应，还抑制对中脑网状刺激的反应。阿普唑仑的脑电图效应约为地西泮的两倍。α-羟基阿普唑仑的药理活性约为阿普唑仑的三分之一。然而，5-氯-2-(3-羟甲基-5-甲基-4H-1,2,4-三唑-4-基)二苯甲酮无药理活性。这些结果表明，阿普唑仑具有苯二氮䓬类药物的特征性药理特性，且活性比地西泮更强。此外，阿普唑仑似乎对中枢5-羟色胺能机制有特定作用。
