Stenberg D, Porkka-Heiskanen T, Toppila J
Department of Physiology, University of Helsinki, Finland.
Eur J Pharmacol. 1993 Jul 20;238(2-3):241-7. doi: 10.1016/0014-2999(93)90853-a.
In order to evaluate the effect of a specific alpha 2-adrenoceptor antagonist, atipamezole, on vigilance, adult cats with implanted electrodes for polygraphy were tested in a double-blind Latin square design. The standard clinical dose (0.1 mg/kg i.m.) of the specific alpha 2-adrenoceptor agonist, medetomidine, promptly induced stuporous sedation. Atipamezole, given 30 min later at 0.2, 0.4 or 0.8 mg/kg i.m., reversed the sedation within 3 min, resulting in complete awareness of the animal. After the small dose of atipamezole, arousal with some motor excitation continued for 6 h, whereas after the larger doses, the physiological sleep-wake cycle returned earlier. Used alone, the preferred dose, 0.4 mg/kg atipamezole i.m., allowed physiological sleep within 33 +/- 9 min, compared to 22 +/- 3 min after saline. Atipamezole thus proved to be a most effective antagonist to sedation with alpha 2-adrenoceptor agonist drugs, without disturbing excitatory effects. Specific alpha 2-adrenoceptor modulating drugs have evident clinical application, as antidotes to overdosage of alpha 2-adrenoceptor agonists, or to terminate their effect after surgical procedures.
为了评估特定的α2-肾上腺素能受体拮抗剂阿替美唑对警觉性的影响,对植入电极用于多导记录的成年猫采用双盲拉丁方设计进行测试。特定的α2-肾上腺素能受体激动剂美托咪定的标准临床剂量(0.1毫克/千克,肌肉注射)迅速诱导出昏睡性镇静。30分钟后,分别以0.2、0.4或0.8毫克/千克的剂量肌肉注射阿替美唑,在3分钟内逆转了镇静作用,使动物完全清醒。小剂量阿替美唑注射后,伴有一定运动兴奋的觉醒持续6小时,而大剂量注射后,生理睡眠-觉醒周期恢复得更早。单独使用时,阿替美唑的首选剂量为0.4毫克/千克肌肉注射,与注射生理盐水后相比,能在33±9分钟内进入生理睡眠状态,而注射生理盐水后为22±3分钟。因此,阿替美唑被证明是α2-肾上腺素能受体激动剂药物镇静的最有效拮抗剂,且不会干扰兴奋作用。特定的α2-肾上腺素能受体调节药物具有明显的临床应用价值,可作为α2-肾上腺素能受体激动剂过量的解毒剂,或在手术后终止其作用。