King D J, Devaney N
Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Br J Clin Pharmacol. 1988 Nov;26(5):607-11. doi: 10.1111/j.1365-2125.1988.tb05303.x.
The cardiovascular, anticholinergic and central effects of single doses of 30, 45 and 60 mg of sibutramine hydrochloride (BTS 54524), a new potential antidepressant, were compared with amitriptyline (50 mg) and placebo given at weekly intervals in a randomised design to six healthy male volunteers. Sibutramine was associated with increases in both supine heart rate and systolic blood pressure at 1, 2 and 6 h after 60 mg (P less than 0.05). Amitriptyline caused a significant 50-60% decrease in salivation compared with placebo at 2 and 6 h but there were no changes with sibutramine. No significant changes in pupil size were detected with either drug. Visual analogue rating scales (VARS) revealed significant drowsiness with amitriptyline but neither sedative nor stimulant effects with sibutramine. Impairments of simple auditory and visual reaction times, visual two-choice reaction time, finger tapping and trail making, measured using an automated test battery, occurred with amitriptyline compared with sibutramine. If sibutramine proves to be an effective antidepressant it should be devoid of anticholinergic or central depressant effects. Chronic dosage studies are indicated to evaluate the clinical significance of its cardiovascular effects.
将一种新的潜在抗抑郁药盐酸西布曲明（BTS 54524）的单剂量30毫克、45毫克和60毫克的心血管、抗胆碱能及中枢效应，与阿米替林（50毫克）和安慰剂进行比较，以随机设计每周给药一次，对6名健康男性志愿者进行研究。60毫克西布曲明给药后1小时、2小时和6小时，仰卧心率和收缩压均升高（P<0.05）。与安慰剂相比，阿米替林在2小时和6小时时导致唾液分泌显著减少50%-60%，但西布曲明无此变化。两种药物均未检测到瞳孔大小有显著变化。视觉模拟评分量表（VARS）显示，阿米替林有显著的嗜睡作用，但西布曲明既无镇静作用也无兴奋作用。与西布曲明相比，使用自动测试组合测量的简单听觉和视觉反应时间、视觉二选反应时间、手指敲击和连线测试，阿米替林均出现损伤。如果西布曲明被证明是一种有效的抗抑郁药，它应该没有抗胆碱能或中枢抑制作用。需要进行长期剂量研究以评估其心血管效应的临床意义。
