Rudorfer M V, Scheinin M, Karoum F, Ross R J, Potter W Z, Linnoila M
Biol Psychiatry. 1984 Feb;19(2):179-93.
Zimelidine (ZIM), a relatively specific serotonin reuptake inhibitor, was administered to 12 hospitalized healthy young male volunteers. Chronic but not acute ZIM caused a modest (23%) but significant elevation of plasma norepinephrine (NE) measured in the standing but not in the supine position. The 24-hr urinary excretion of NE itself was unchanged on chronic drug, whereas "whole-body" NE turnover was reduced by 1 week of ZIM, as evidenced by lowered excretion rates (both individually and summed with NE) of the metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NM), and vanillylmandelic acid. Lack of effect of ZIM on the NM/MHPG excretion ratio (which is increased by desipramine) indicated that ZIM and its major metabolite, horzimelidine (NZIM) are not acting by NE reuptake blockade. These data are consistent with modulating serotonergic influence on the noradrenergic system. Reduction of NE turnover and increasing the efficiency of the NE neurotransmission may be a common pathway of all clinically effective antidepressant treatments.
齐美利定（ZIM）是一种相对特异性的5-羟色胺再摄取抑制剂，被给予12名住院的健康年轻男性志愿者。长期而非急性给予ZIM会导致站立位而非仰卧位时血浆去甲肾上腺素（NE）适度（23%）但显著升高。长期用药时，NE自身的24小时尿排泄量未改变，而“全身”NE周转率在使用ZIM 1周后降低，这可由代谢产物3-甲氧基-4-羟基苯乙二醇（MHPG）、去甲变肾上腺素（NM）和香草扁桃酸的排泄率降低（单独及与NE总和）来证明。ZIM对NM/MHPG排泄率比值（地昔帕明可使其升高）无影响，表明ZIM及其主要代谢产物羟齐美利定（NZIM）并非通过阻断NE再摄取起作用。这些数据与调节5-羟色胺能对去甲肾上腺素能系统的影响一致。降低NE周转率及提高NE神经传递效率可能是所有临床有效抗抑郁治疗的共同途径。
