Moxonidine and cognitive function: interactions with moclobemide and lorazepam
Moxonidine and cognitive function: interactions with moclobemide and lorazepam
复制标题
莫索尼定和认知功能：与吗氯贝胺和劳拉西泮的相互作用
DOI：
10.1007/s002280050300
复制
发表时间：
1997
影响因子：
2.9
通讯作者：
H. Küppers
中科院分区：
文献类型：
--
作者：
K. Wesnes;Pippa M. Simpson;B. Jansson;A. Grahnén;H. Weimann;H. Küppers
摘要目的：莫索尼定是新一代中枢性降压药。它与I1-咪唑啉受体结合，通过降低全身血管阻力发挥抗高血压活性，而心输出量保持不变甚至略有增加。莫索尼定用于治疗轻度至中度高血压。典型剂量为 0.4 至 2.0mg，早上服用一剂，或早晚分次服用。
方法：在两项双盲、随机、安慰剂对照、双向交叉研究中，对总共 48 名健康志愿者进行了两项双盲、随机、安慰剂对照、双向交叉研究，研究了莫索尼定 0.4mg 每日一次与吗氯贝胺或劳拉西泮联用的效果。每项研究均进行安全性评估，包括研究前和研究后血压、心率、心电图、血液学、血液生化和尿液分析的测量，以及不良事件的记录。
结果：在第一项研究中，发现单独使用莫索尼定会对 4 小时和 6 小时的警觉检测速度产生微小但具有统计学意义的损害。还观察到主观警觉性降低。重复服用莫索尼定会损害记忆扫描性能。这些结果在第二项研究中没有得到重复，在第二项研究中，单独使用莫索尼定可以在 4 小时和 6 小时时改善即时单词回忆。当莫索尼定与吗氯贝胺共同给药时，没有观察到相互作用。莫索尼定与劳拉西泮同时服用时，会与三项需要高度注意力的任务产生相互作用：选择、简单反应时间和数字警觉表现；记忆任务；即时单词回忆、延迟单词回忆准确度；研究 1 中总共报告了 47 例不良事件。莫索尼定导致收缩压和舒张压略有下降。在研究 2 中，总共报告了 55 起不良事件。在这两项试验中，最常报告的事件是疲劳和口干，后者仅在莫索尼定治疗下发生。在这两项研究中，均未观察到血压、脉率和实验室检查方面的临床相关变化，也没有任何证据表明莫索尼定与吗氯贝胺或劳拉西泮之间存在任何相互作用。
结论：发现莫索尼定在健康志愿者中是安全的且耐受性良好。然而，当莫索尼定与劳拉西泮 1mg 联合给药时，注意力任务的损害更大。当莫索尼定与劳拉西泮同时服用时，应考虑这些影响，尽管这些影响比单剂量劳拉西泮 2mg 产生的影响要小。
AbstractObjective: Moxonidine represents a new generation of centrally acting antihypertensive drugs. It binds to I1-imidazoline receptors and exerts its antihypertensive activity through a reduction in systemic vascular resistance, while cardiac output remains unchanged or even increases slightly. Moxonidine is prescribed for the treatment of mild to moderate hypertension. Typical doses are 0.4 to 2.0 mg given as one dose in the morning or as divided doses in the morning and evening.
Methods: The effects of moxonidine 0.4 mg once daily in combination with moclobemide or lorazepam were investigated in two, double-blind, randomised, placebo-controlled, two-way crossover studies in a total of 48 healthy volunteers. Safety assessments were made in each study and included pre- and post-study measurement of blood pressure, heart rate, ECG, haematology, blood biochemistry, and urinalysis, and recording of adverse events.
Results: In the first study, moxonidine alone was found to produce small but statistically significant impairments of vigilance detection speed at 4 h and 6 h. Lowering of subjective alertness was also observed. Repeat dosing with moxonidine produced an impairment of memory scanning performance. These findings were not reproduced in the second study, in which moxonidine alone produced an improvement in immediate word recall at 4 h and 6 h.No interactions were observed when moxonidine was co-administered with moclobemide. Moxonidine, when co-administered with lorazepam, produced interactions with three tasks requiring high levels of attention: choice, simple reaction time and digit vigilance performance; memory tasks; immediate word recall, delayed word recall accuracy; and visual tracking.A total of 47 adverse events were reported in study 1. Moxonidine produced a slight decrease of systolic and diastolic blood pressure. In study 2, a total of 55 adverse events were reported. In both trials, the most frequently reported events were tiredness and dryness of mouth, the latter occurring only under the moxonidine treatment. There were no clinically relevant changes observed in blood pressure, pulse rate, and laboratory tests in either study, nor was there any evidence of any interaction between moxonidine and either moclobemide or lorazepam.
Conclusion: Moxonidine was found to be safe and well tolerated in healthy volunteers. However, the impairments on attentional tasks were greater when moxonidine was co-administered with lorazepam 1 mg. These effects should be considered when moxonidine is co-dosed with lorazepam, although they were smaller than would have been produced by a single dose of lorazepam 2 mg.
影响因子：
3
作者：
M. Haxhiu;I. Dreshaj;S. Schäfer;P. Ernsberger
通讯作者：
M. Haxhiu;I. Dreshaj;S. Schäfer;P. Ernsberger