Petry N M, Bickel W K, Huddleston J, Tzanis E, Badger G J
Department of Psychiatry, University of Vermont, Burlington 05401, USA.
Drug Alcohol Depend. 1998 Apr 1;50(2):129-36. doi: 10.1016/s0376-8716(98)00026-x.
This study compared the subjective, physiological and psychomotor effects of a novel muscarinic analgesic (LY297802) and oral morphine in healthy volunteers. Nine, non-dependent, occasional drug users participated in nine experimental sessions in which they received the following conditions: placebo, 0.1, 0.3, 0.56 and 1 mg of oral LY297802 and 10, 30, 56 and 100 mg of oral morphine. Subjective drug effects were assessed using the Visual Analog Scale (VAS), the Addiction Research Center Inventory (ARCI) and subjective and objective agonist and antagonist scales of the Adjective Rating Scale (ARS). These measures were collected 30 min before and every 30 min post drug administration for a 4-h period. Psychomotor performance was evaluated using the Digit Symbol Substitution Test (DSST) at these same time intervals. Physiological measures were collected continuously throughout the sessions. Oral morphine produced significant increases in some subjective effects scales, including elevations on the VAS, ARCI and ARS. In contrast, LY297802 did not engender changes different from placebo on any of these indices. Morphine produced significant dose-dependent effects in DSST performance, heart rate, blood oxygen saturation and pupil diameter. LY297802 significantly and dose dependently increased heart rate, mean arterial pressure and diastolic blood pressure. These results suggest that LY297802 does not induce subjective effects similar to morphine, but that it has some significant physiological effects.
本研究比较了一种新型毒蕈碱类镇痛药(LY297802)和口服吗啡对健康志愿者的主观、生理及精神运动效应。9名非依赖型、偶尔使用药物的受试者参加了9次实验,在实验中他们接受了以下几种情况:安慰剂、0.1毫克、0.3毫克、0.56毫克和1毫克的口服LY297802以及10毫克、30毫克、56毫克和100毫克的口服吗啡。使用视觉模拟量表(VAS)、成瘾研究中心量表(ARCI)以及形容词评定量表(ARS)的主观和客观激动剂及拮抗剂量表评估主观药物效应。在给药前30分钟以及给药后4小时内每30分钟收集一次这些测量数据。在相同时间间隔使用数字符号替换测验(DSST)评估精神运动表现。在整个实验过程中持续收集生理测量数据。口服吗啡使一些主观效应量表有显著增加,包括VAS、ARCI和ARS升高。相比之下,LY297802在这些指标上未产生与安慰剂不同的变化。吗啡在DSST表现、心率、血氧饱和度和瞳孔直径方面产生显著的剂量依赖性效应。LY297802显著且剂量依赖性地增加心率、平均动脉压和舒张压。这些结果表明,LY297802不会诱发与吗啡相似的主观效应,但具有一些显著的生理效应。