Sbirrazzuoli V, Drici M, Garraffo R, Candito M, Gibelin P, Morand P, Lapalus P
Department of Clinical Pharmacology, Nice, France.
Drugs Exp Clin Res. 1989;15(5):223-9.
Dilevalol (R,R'-isomer of labetalol) is an antihypertensive agent combining non-specific beta blockade with peripheral vasodilatation due to beta 2-receptor agonism. The aim of this study was to determine the effects of chronic dilevalol administration on lymphocyte beta 2-adrenoceptor density. The investigation was conducted as a double-blind, placebo-controlled comparison. Ten days of chronic dilevalol (400 mg) or placebo treatment was administered to 12 healthy normotensive volunteers. Clinical and biochemical parameters: heart rate (HR) systolic and diastolic blood pressure (SBP, DBP), electrocardiogram, norepinephrine (NE), epinephrine (E), MHPG (3-methoxy-4-hydroxyphenylethylene glycol; one of the major brain metabolites of NE) were analysed on the first day (D1) before (H0) and 3 h after oral treatment (H3) and on the tenth day (D10). Clinical results showed no significant changes in HR, DBP, SBP in the two groups (placebo, n = 6; dilevalol, n = 6). NE increased 3 h after the first oral dilevalol intake (p less than 0.05). This increase is greater than that due to the circadian variation observed in the placebo group. Acute dilevalol treatment seems to increase the plasma circulating NE level, which returns to normal values after 10 days of chronic treatment. Binding assays were performed before and after 10 days of treatment. In the placebo group, no change in beta-adrenoceptor density was observed (36.6 +/- 8.3 versus 38.3 +/- 9.4 femtomol/mg of protein). Lymphocyte beta-adrenoceptor density (Bmax) significantly decreased after 10 days of dilevalol treatment without any changes in affinity (KD). Results were 40.3 +/- 11.6 (D1) and 30 +/- 7.6 (D10) (p less than 0.05). It was concluded that dilevalol down-regulated lymphocyte beta 2-adrenoceptor density, suggesting that beta 2 agonism of dilevalol is predominant.
双醋洛尔（拉贝洛尔的R，R'-异构体）是一种抗高血压药物，它结合了非特异性β受体阻断作用和因β2受体激动引起的外周血管舒张作用。本研究的目的是确定长期服用双醋洛尔对淋巴细胞β2-肾上腺素能受体密度的影响。该研究以双盲、安慰剂对照的方式进行比较。对12名健康的血压正常志愿者进行了为期10天的双醋洛尔（400毫克）或安慰剂治疗。在第一天（D1）口服治疗前（H0）和3小时后（H3）以及第十天（D10）分析临床和生化参数：心率（HR）、收缩压和舒张压（SBP、DBP）、心电图、去甲肾上腺素（NE）、肾上腺素（E）、MHPG（3-甲氧基-4-羟基苯乙二醇；NE的主要脑代谢产物之一）。临床结果显示两组（安慰剂组，n = 6；双醋洛尔组，n = 6）的HR、DBP、SBP均无显著变化。首次口服双醋洛尔后3小时NE升高（p < 0.05）。这种升高大于安慰剂组观察到的昼夜变化。急性双醋洛尔治疗似乎会增加血浆中循环NE水平，而在长期治疗10天后会恢复到正常水平。在治疗10天前后进行结合试验。在安慰剂组中，未观察到β-肾上腺素能受体密度的变化（36.6±8.3对38.3±9.4飞摩尔/毫克蛋白质）。双醋洛尔治疗10天后淋巴细胞β-肾上腺素能受体密度（Bmax）显著降低，亲和力（KD）无任何变化。结果分别为40.3±11.6（D1）和30±7.6（D10）（p < 0.05）。得出的结论是，双醋洛尔下调了淋巴细胞β2-肾上腺素能受体密度，表明双醋洛尔的β2激动作用占主导。
