Tsuchihashi H, Aono J, Nagatomo T, Kawada T, Ohta H, Imai S
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Jpn J Pharmacol. 1987 Nov;45(3):349-56. doi: 10.1254/jjp.45.349.
To assess the importance of anti-adrenergic and anti-serotonergic activities of bunitrolol for its efficacy as an antihypertensive and antianginal agent, effects of this substance on the binding of adrenergic and serotonergic agents to the respective receptors of the rat brain, rat heart, dog brain, and/or dog aorta were examined using the radioligand binding assay methods. In addition, the pA2 values of bunitrolol as an antagonist against the positive chronotropic and inotropic actions (beta 1-adrenoceptor) of isoproterenol were also determined by pharmacological methods using the isolated guinea pig atria. To assess the specificity, pA2 values were also obtained in the isolated trachea (beta 2-adrenoceptor) using isoproterenol as an agonist and in the isolated aorta from the guinea pig and the rat using phenylephrine as an agonist (alpha 1-adrenoceptor). A strong inhibition by bunitrolol of 3H-dihydroalprenolol (3H-DHA) binding to beta-adrenoceptors was observed, while the inhibition of 3H-prazosin binding to alpha 1-adrenoceptors, 3H-serotonin binding to 5HT1-receptors. 3H-p-aminoclonidine binding to alpha 2-adrenoceptors, and 3H-ketanserin binding to 5HT2-receptors were found to be very weak. The rank order of antagonistic potencies of bunitrolol against the adrenergic receptors as assessed with pA2 values were beta 1 greater than beta 2 much greater than alpha 1. From these two different types of experiments, it is clear that the antihypertensive and antianginal effects of bunitrolol are mainly due to its beta-blocking actions, with the alpha 1-blocking action of this drug playing a minor role.
为评估布尼洛尔的抗肾上腺素能和抗5-羟色胺能活性对其作为抗高血压和抗心绞痛药物疗效的重要性，使用放射性配体结合分析方法检测了该物质对肾上腺素能和5-羟色胺能药物与大鼠脑、大鼠心脏、犬脑和/或犬主动脉各自受体结合的影响。此外，还通过药理学方法，使用离体豚鼠心房，测定了布尼洛尔作为异丙肾上腺素正性变时和变力作用（β1-肾上腺素受体）拮抗剂的pA2值。为评估特异性，还使用异丙肾上腺素作为激动剂，在离体气管（β2-肾上腺素受体）中，以及使用去氧肾上腺素作为激动剂，在豚鼠和大鼠的离体主动脉中（α1-肾上腺素受体）获得了pA2值。观察到布尼洛尔对3H-二氢阿普洛尔（3H-DHA）与β-肾上腺素受体结合有强烈抑制作用，而对3H-哌唑嗪与α1-肾上腺素受体结合、3H-5-羟色胺与5HT1-受体结合、3H-p-氨基可乐定与α2-肾上腺素受体结合以及3H-酮色林与5HT2-受体结合的抑制作用非常弱。以pA2值评估，布尼洛尔对肾上腺素能受体的拮抗效力顺序为β1＞β2＞＞α1。从这两种不同类型的实验可以看出，布尼洛尔的抗高血压和抗心绞痛作用主要归因于其β-阻断作用，该药物的α1-阻断作用起次要作用。
