COMPARISON OF THE MONOAMINE-OXIDASE INHIBITING PROPERTIES OF 2 REVERSIBLE AND SELECTIVE MONOAMINE OXIDASE-A INHIBITORS MOCLOBEMIDE AND TOLOXATONE, AND ASSESSMENT OF THEIR EFFECT ON PSYCHOMETRIC PERFORMANCE IN HEALTHY-SUBJECTS
COMPARISON OF THE MONOAMINE-OXIDASE INHIBITING PROPERTIES OF 2 REVERSIBLE AND SELECTIVE MONOAMINE OXIDASE-A INHIBITORS MOCLOBEMIDE AND TOLOXATONE, AND ASSESSMENT OF THEIR EFFECT ON PSYCHOMETRIC PERFORMANCE IN HEALTHY-SUBJECTS
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DOI：
10.1111/j.1365-2125.1990.tb05445.x
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发表时间：
1990-12-01
影响因子：
3.4
通讯作者：
PUECH, AJ
中科院分区：
文献类型：
--
作者：
BERLIN, I;ZIMMER, R;PUECH, AJ
在12名健康受试者中进行的双盲安慰剂对照交叉研究中，比较了两种可逆的主要单胺氧化酶-A（MAO-A）抑制剂吗氯贝胺（150 mg，每日3次）和托洛沙酮（400-200-400 mg，每日1次）对单胺代谢物和心理测量表现的影响。吗氯贝胺/托洛沙酮/安慰剂给药7天后，受试者在第8天住院24天。每隔2 h采血测定血浆去甲肾上腺素（NA）、3，4-二羟基苯乙二醇（DHPG）、高香草酸（HVA）和5-羟基吲哚乙酸（5-HIAA）。采集尿液，用于测量去甲甲肾上腺素和3-甲氧基酪胺排泄。在每次服药前（早上、中午、晚上）评估心理测量性能（短期和长期记忆、临界闪烁融合频率、选择反应时间）和主观感受。与安慰剂相比，两种可逆性单胺氧化酶抑制剂均降低DHPG和HVA的血浆浓度。吗氯贝胺组DHPG（0 - 24 h AUC）总体下降44%，托洛沙酮组下降12%（P < 0.001），吗氯贝胺组和托洛沙酮组HVA总体下降分别为38%和20%（P < 0.005）。在下一次药物摄入前，通过血浆DHPG浓度的降低来判断，吗氯贝胺对MAO-A的抑制作用与安慰剂有显著差异，但与托洛沙酮无显著差异。吗氯贝胺（而不是托洛沙酮）对5-羟色胺（5-HT）的脱氨基作用产生中度但显著的抑制作用，这通过血浆5-HIAA浓度的下降来判断。两种药物均不影响血浆NA浓度。在吗氯贝胺组中观察到去甲美坦利的尿排泄显著增加，在托洛沙酮组中观察到程度较小。吗氯贝胺可显著增加3-甲氧基酪胺的尿排泄量，而托洛沙酮则无此作用。吗氯贝胺和托洛沙酮均未改变受试者的记忆功能、警觉性、主观感受或睡眠特征。
The effects of two reversible, predominantly monoamine oxidase-A (MAO-A) inhibitors, moclobemide (150 mg three times daily) and toloxatone (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects. After 7 days of moclobemide/toloxatone/placebo administration subjects were hospitalized for 24 on day 8. Blood samples were drawn every 2 h for determination of plasma noradrenaline (NA), 3,4-dihydroxyphenylglycol (DHPG), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA). Urine was collected for measurements of normetanephrine and 3-methoxytyramine excretion. Psychometric performance (short- and long-term memory, critical flicker fusion frequency, choice reaction time) and subjective feelings were assessed before each drug intake (in the morning, at noon, in the evening). Compared with placebo, both reversible monoamine oxidase inhibitors decreased the plasma concentration of DHPG and HVA. The overall fall in DHPG (AUC from 0 to 24 h) was 44% during moclobemide and 12% during toloxatone (P < 0.001) and the overall decrease in HVA was 38% and 20% (P < 0.005) on moclobemide and toloxatone, respectively. Before the next drug intake, MAO-A inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with toloxatone. Moclobemide, but not toloxatone, exerted a moderate, but significant inhibition of the deamination of 5-hydroxytryptamine (5-HT) as judged by the fall in plasma 5-HIAA concentration. Neither drug influenced plasma NA concentration. A significant rise in urinary excretion of normetanephrine was observed on moclobemide and to a lesser extent on toloxatone. The urinary excretion of 3-methyoxytyramine was significantly raised by moclobemide but not by toloxatone. Neither moclobemide nor toloxatone altered memory function, vigilance, subjective feelings or sleep characteristics of the subjects.