Cutler N R, Haxby J, Kay A D, Narang P K, Lesko L J, Costa J L, Ninos M, Linnoila M, Potter W Z, Renfrew J W
Arch Neurol. 1985 Aug;42(8):744-8. doi: 10.1001/archneur.1985.04210090008003.
Neuropsychological and neurochemical effects of zimeldine, a relatively specific serotonin reuptake blocker, were examined in four patients with clinically diagnosed Alzheimer's disease, in a double-blind, placebo-controlled, crossover study. Individualized doses of zimeldine were administered to achieve target plasma zimeldine concentrations of approximately 50 (low) to 100 (high) ng/mL. Overall, there was no significant effect of zimeldine on memory or reaction time measures as compared with placebo. The drug significantly reduced (by up to 38%) 5-hydroxyindoleacetic acid concentrations in the cereobrospinal fluid and almost abolished (90% reduction) platelet serotonin uptake. Cerebrospinal fluid concentrations of 3-methoxy-4-hydroxy-phenylglycol, a major metabolite of norepinephrine, and homovanillic acid, the major metabolite of dopamine, were not altered. Our findings indicate that alterations in central and peripheral serotoninergic function by a serotonin reuptake blocker (zimeldine) are unaccompanied by measurable changes in memory and/or reaction time in patients presumed to have Alzheimer's disease.
在一项双盲、安慰剂对照的交叉研究中，对4例临床诊断为阿尔茨海默病的患者，研究了相对特异性的5-羟色胺再摄取阻滞剂齐美利定的神经心理学和神经化学效应。给予个体化剂量的齐美利定，以达到血浆齐美利定浓度约50（低）至100（高）ng/mL的目标。总体而言，与安慰剂相比，齐美利定对记忆或反应时间测量无显著影响。该药物显著降低（高达38%）脑脊液中5-羟吲哚乙酸浓度，并几乎完全消除（降低90%）血小板5-羟色胺摄取。去甲肾上腺素的主要代谢产物3-甲氧基-4-羟基苯乙二醇以及多巴胺的主要代谢产物高香草酸的脑脊液浓度未改变。我们的研究结果表明，在推测患有阿尔茨海默病的患者中，5-羟色胺再摄取阻滞剂（齐美利定）引起的中枢和外周5-羟色胺能功能改变并未伴随记忆和/或反应时间的可测量变化。
