Moore N, Fresel J, Joannidès R, Compagnon P, Thuillez C
VACOMED, Service de Pharmacologie Clinique, CHU Rouen, Boisguillaume, France.
Blood Press Suppl. 1994;4:7-12.
Urapidil is an antihypertensive agent known to have central 5HT1A agonistic properties in addition to alpha-1 blocking effects. To assess the importance of these effects, we compared the hemodynamic effects of a single oral dose of urapidil (U, 60 mg) with those of prazosin (Pr, 2 mg), clonidine (Cl, 0.15 mg), and placebo (Pl), at rest, during orthostatic tilt, and during submaximal graded bicycle exercise tests, in a double-blind randomised crossover study in 24 healthy male volunteers. The variables studied were heart rate, mean blood pressure, cardiac index by bioimpedance, systemic vascular resistance index (SVRI), and plasma norepinephrine. Baseline values before drug administration were identical. At rest, during tilt, and during identical exercise, compared to placebo, urapidil and prazosin caused similar decreases in SVRI, with a smaller increase in HR after urapidil than after prazosin (p < 0.01), and without any difference in BP. Both drugs increased norepinephrine in a similar manner. In contrast, clonidine decreased blood pressure (p < 0.01) and norepinephrine (p < 0.01) with no difference in heart rate or SVRI. In conclusion, at rest, during tilt and during exercise, urapidil and prazosin have similar vasodilating effects, but the sympathetic stimulation is less and the parasympathetic stimulation greater after urapidil than after prazosin, probably indicating a centrally acting effect of urapidil. However, the sympathoinhibitory effect of urapidil is less marked than that of clonidine.
乌拉地尔是一种抗高血压药物，除具有α1受体阻滞作用外，还具有中枢5HT1A激动特性。为评估这些作用的重要性，在一项双盲随机交叉研究中，我们比较了24名健康男性志愿者在静息状态、直立倾斜试验及次极量分级自行车运动试验期间，单次口服乌拉地尔（U，60mg）与哌唑嗪（Pr，2mg）、可乐定（Cl，0.15mg）及安慰剂（Pl）的血流动力学效应。所研究的变量包括心率、平均血压、生物阻抗法测定的心脏指数、全身血管阻力指数（SVRI）及血浆去甲肾上腺素。给药前的基线值相同。在静息状态、倾斜试验及相同运动期间，与安慰剂相比，乌拉地尔和哌唑嗪使SVRI出现相似程度的降低，乌拉地尔给药后心率升高幅度小于哌唑嗪（p<0.01），血压无差异。两种药物使去甲肾上腺素升高的方式相似。相比之下，可乐定使血压（p<0.01）和去甲肾上腺素（p<0.01）降低，心率和SVRI无差异。总之，在静息状态、倾斜试验及运动期间，乌拉地尔和哌唑嗪具有相似的血管舒张作用，但乌拉地尔给药后交感神经刺激小于哌唑嗪，副交感神经刺激大于哌唑嗪，这可能表明乌拉地尔具有中枢作用。然而，乌拉地尔的交感神经抑制作用不如可乐定明显。
