Leckman J F, Maas J W, Heninger G R
Eur J Pharmacol. 1981 Mar 12;70(2):111-20. doi: 10.1016/0014-2999(81)90205-3.
To test the acute effects of clonidine on plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), the major metabolite of brain norepinephrine (NE), and to examine the relationship between plasma MHPG and concurrently measured blood pressure variables, we performed a series of 31 double blind, placebo controlled, test days in which clonidine (1 and 5 micrograms/kg) or placebo was administered (p.o. at 9:00 a.m.) to six fasting normotensive male subjects. Three h following the 5 micrograms/kg clonidine dose, plasma MHPG reached a nadir significantly below both baseline and placebo levels (P less than 0.05). Mean MHPG concentrations were significantly correlated with diastolic blood pressure (sitting: r = 0.46, df = 88, P less than 0.00001; standing r = 0.49, df = 73, P less than 0.00001). Unexpectedly, this relationship was independent of clonidine dose and sampling time. Under drug-free conditions, the correlation between plasma free MHPG and diastolic blood pressure remained significant (sitting: r = 0.43, df = 40, P = 0.003; standing: r = 0.46, df = 33, P = 0.006). The findings are considered in light of evidence implicating brain NE systems in the regulation of blood pressure.
为了测试可乐定对3-甲氧基-4-羟基苯乙二醇（MHPG，脑去甲肾上腺素（NE）的主要代谢产物）血浆水平的急性影响，并研究血浆MHPG与同时测量的血压变量之间的关系，我们对6名空腹血压正常的男性受试者进行了一系列31个双盲、安慰剂对照的测试日，在上午9:00口服给予可乐定（1和5微克/千克）或安慰剂。在给予5微克/千克可乐定剂量后3小时，血浆MHPG降至最低点，显著低于基线和安慰剂水平（P<0.05）。平均MHPG浓度与舒张压显著相关（坐位：r = 0.46，自由度 = 88，P<0.00001；站位：r = 0.49，自由度 = 73，P<0.00001）。出乎意料的是，这种关系与可乐定剂量和采样时间无关。在无药物条件下，血浆游离MHPG与舒张压之间的相关性仍然显著（坐位：r = 0.43，自由度 = 40，P = 0.003；站位：r = 0.46，自由度 = 33，P = 0.006）。根据涉及脑NE系统参与血压调节的证据对这些发现进行了考量。
