SEDATIVE AND CARDIOVASCULAR EFFECTS OF MEDETOMIDINE, A NOVEL SELECTIVE ALPHA-2-ADRENOCEPTOR AGONIST, IN HEALTHY-VOLUNTEERS
SEDATIVE AND CARDIOVASCULAR EFFECTS OF MEDETOMIDINE, A NOVEL SELECTIVE ALPHA-2-ADRENOCEPTOR AGONIST, IN HEALTHY-VOLUNTEERS
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DOI：
10.1111/j.1365-2125.1987.tb03196.x
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发表时间：
1987-10-01
影响因子：
3.4
通讯作者：
SCHEININ, H
中科院分区：
文献类型：
--
作者：
SCHEININ, M;KALLIO, A;SCHEININ, H
在一项双盲、安慰剂对照研究中，将单次静脉内剂量（25、50和100 μ g）的美托咪定（MPV-785，一种咪唑衍生物）（一种选择性α 2-肾上腺素受体激动剂）给予8名健康男性志愿者。观察到以下剂量相关效应，所有这些效应都与药物对α 2-肾上腺素受体的激动作用相一致：收缩压和舒张压（最大18/11 mm Hg）、心率（最大10次/min）、唾液分泌（最大84%）和血浆中去甲肾上腺素水平（最大70%）的降低。通过主观和客观（临界闪烁融合阈值）评估，还观察到剂量依赖性镇静或警戒受损，最高剂量实际上诱导了5例受试者的睡眠。所观察到的效果与先前在静脉内施用中枢作用的抗高血压α 2-肾上腺素受体激活药物可乐定后观察到的效果大体一致，但持续时间较短。不能确定位于外周组织和中枢神经系统中的α 2-肾上腺素受体对于药物的心血管作用的相对重要性，但化合物的高脂溶性和镇静作用的快速起效有利于主要中枢组分。美托咪啶可能是研究人的α 2-肾上腺素能受体的生理学和药理学的有用工具，此外，应该在与交感神经元活性增加有关的病理状况中研究该化合物的治疗和诊断用途。
Single intravenous doses (25, 50 and 100 .mu.g) of medetomidine (MPV-785, an imidazole derivative), a selective .alpha.2-adrenoceptor agonist, were administered to eight healthy male volunteers in a double-blind, placebo-controlled study. The following dose-related effects, all of which were compatible with an agonistic action of the drug at .alpha.2-adrenoceptors, were noted: reductions of systolic and diastolic blood pressure (maximum 18/11 mm Hg), heart rate (maximum 10 beats min-1), saliva secretion (maximum 84%) and noradrenaline levels in plasma (maximum 70%). Dose-dependent sedation or impairment of vigilance was also observed, both by subjective and objective (critical flicker fusion threshold) assessments, with the highest dose actually inducing sleep in five of the subjects. The observed effects were in general agreement with those previously seen after intravenous administration of the centrally acting antihypertensive .alpha.2-adrenoceptor activating drug, clonidine, but of a shorter duration. The relative importance of .alpha.2-adrenoceptors located in peripheral tissues and in the central nervous system for the drug''s cardiovascular effects could not be determined, but the high lipid solubility of the compound and the rapid onset of sedation are in favour of a major central component. Medetomidine may be a useful tool for the investigation of the physiology and pharmacology of .alpha.2-adrenoceptors in man. In addition, the therapeutic and diagnostic uses of the compound should be investigated in pathological conditions related to increased sympathetic neuronal activity.