Lemmer B, Neumann G
Arzneimittelforschung. 1987 Mar;37(3):321-5.
The effects of seven beta-receptor blocking drugs differing in lipophilicity by 3.5 orders of magnitude (propranolol, bupranolol, oxprenolol, metoprolol, sotalol, practolol, atenolol) were studied on the circadian rhythm in motor activity of light-dark-synchronized (light (L): 7-19 h, dark (D): 19-7 h) male rats. Motor activity after i.p. injection of saline or of the racemic mixtures of all drugs and the isomers of propranolol, bupranolol and practolol was measured in groups of 5 rats with a motimeter. Two doses of either drug were injected either at 7:30 a.m. in L or at 7:30 p.m. in D. In L the drugs did either not affect motor activity or even increased motility in comparison to saline. No dosage-dependency was observed in the drug effects in L. In contrast, during D a dosage-dependent decrease in motor activity was found for all compounds. ED50-values of decrease in motility during D were negatively correlated with lipophilicity (partition coefficient) of the compounds. No significant difference was found in the ED50-values of the isomers studied. The results clearly demonstrate a circadian phase dependency in the effects of beta-receptor blocking drugs on motor activity of rats. A dosage-dependent central depressant effect of the drugs could be observed only in D. It is concluded that the central depressant effects of beta-receptor blocking drugs are mainly due to the non-specific, lipophilic property of the drugs and not brought about by a specific blockade of central beta-adrenoceptors.
研究了七种亲脂性相差3.5个数量级的β受体阻断药物（普萘洛尔、布普洛尔、氧烯洛尔、美托洛尔、索他洛尔、普拉洛尔、阿替洛尔）对光暗同步（光照（L）：7 - 19时，黑暗（D）：19 - 7时）雄性大鼠运动活动昼夜节律的影响。腹腔注射生理盐水或所有药物的外消旋混合物以及普萘洛尔、布普洛尔和普拉洛尔的异构体后，用活动计测量5只大鼠组的运动活动。两种剂量的任一药物分别在上午7:30的光照期或下午7:30的黑暗期注射。在光照期，与生理盐水相比，这些药物要么不影响运动活动，甚至增加运动性。在光照期未观察到药物效应的剂量依赖性。相反，在黑暗期，所有化合物均出现运动活动的剂量依赖性降低。黑暗期运动性降低的ED50值与化合物的亲脂性（分配系数）呈负相关。所研究异构体的ED50值未发现显著差异。结果清楚地表明β受体阻断药物对大鼠运动活动的影响存在昼夜相依赖性。仅在黑暗期可观察到药物的剂量依赖性中枢抑制作用。结论是β受体阻断药物的中枢抑制作用主要归因于药物的非特异性亲脂性特性，而非由中枢β肾上腺素受体特异性阻断引起。
