Palluk R, Hoefke W
Department of Pharmacology, Boehringer Ingelheim KG, F.R.G.
Arch Int Pharmacodyn Ther. 1989 Sep-Oct;301:215-27.
Adimolol is a new antihypertensive agent with strong nonselective beta- and moderate alpha-adrenolytic properties. In order to elucidate whether the alpha-adrenoceptor blockade by adimolol may contribute to the blood pressure lowering action of the compound, we tested 1) the effect on heart rate and blood pressure in conscious spontaneously hypertensive rats after oral administration and 2) the influence on the pressor effect of intra-arterially injected noradrenaline in autoperfused rat hindquarters after i.v. administration. Adimolol was compared with propranolol, labetalol, prazosin and combinations of propranolol plus low-dose prazosin. In conscious spontaneously hypertensive rats, labetalol, propranolol plus low-dose prazosin and adimolol lowered blood pressure considerably in parallel with heart rate. Propranolol alone acutely lowered heart rate, but not blood pressure. Low-dose prazosin alone lowered blood pressure and heart rate only moderately. In autoperfused hindquarters, the pressor-response curve to noradrenaline was dose-dependently shifted to the left by propranolol and to the right by labetalol or prazosin. The leftward shift by propranolol could be antagonized dose-dependently by addition of low doses of prazosin. Adimolol, at doses of 0.1, 10 and 20 mg/kg, did not significantly influence the pressor-response curve to noradrenaline in this model, whereas a slight but significant shift to the left was observed with 1 mg/kg. In summary, the cardiovascular effects of adimolol in rats cannot completely be explained by beta-adrenoceptor blockade. They can be mimicked by the concomitant administration of a beta-adrenoceptor blocking and an alpha-adrenoceptor blocking agent. We conclude that the alpha-adrenolytic activity of adimolol can be demonstrated in vivo and may contribute to the blood pressure lowering action of the compound in rats.
阿地洛尔是一种新型抗高血压药物，具有强效非选择性β-肾上腺素能阻断及中度α-肾上腺素能阻断特性。为阐明阿地洛尔的α-肾上腺素能受体阻断作用是否有助于该化合物的降压作用，我们进行了如下实验：1）口服给药后对清醒自发性高血压大鼠心率和血压的影响；2）静脉给药后对自灌注大鼠后肢动脉注射去甲肾上腺素升压效应的影响。将阿地洛尔与普萘洛尔、拉贝洛尔、哌唑嗪以及普萘洛尔加小剂量哌唑嗪的组合进行比较。在清醒自发性高血压大鼠中，拉贝洛尔、普萘洛尔加小剂量哌唑嗪和阿地洛尔能显著降低血压，同时伴有心率下降。单独使用普萘洛尔可急性降低心率，但不降低血压。单独使用小剂量哌唑嗪仅适度降低血压和心率。在自灌注后肢中，普萘洛尔使去甲肾上腺素的升压反应曲线剂量依赖性向左移动，而拉贝洛尔或哌唑嗪则使其向右移动。普萘洛尔引起的向左移动可被小剂量哌唑嗪剂量依赖性拮抗。在该模型中，0.1、10和20mg/kg剂量的阿地洛尔对去甲肾上腺素的升压反应曲线无显著影响，而1mg/kg剂量时可观察到轻微但显著的向左移动。总之，阿地洛尔在大鼠中的心血管作用不能完全用β-肾上腺素能受体阻断来解释。它们可通过同时给予β-肾上腺素能受体阻断剂和α-肾上腺素能受体阻断剂来模拟。我们得出结论，阿地洛尔的α-肾上腺素能阻断活性在体内可得到证实，可能有助于该化合物在大鼠中的降压作用。
