Naito K, Nagao T, Otsuka M, Harigaya S, Nakajima H
Jpn J Pharmacol. 1985 Jul;38(3):235-41. doi: 10.1254/jjp.38.235.
Denopamine is a new orally active cardiotonic agent. The present experiment was carried out to characterize the binding affinity and selectivity of this drug for beta-adrenergic receptor subtypes. Binding studies were performed using 3H-dihydroalprenolol as the radioligand. Binding affinities of denopamine and some beta-agonists for rat heart membranes (KiH), which contain predominantly the beta 1-subtype, were in the order of isoproterenol (Iso, 14.1 nM) greater than prenalterol (158) greater than norepinephrine (Nor, 227) greater than or equal to epinephrine (Epi, 248) greater than denopamine (545) greater than or equal to dobutamine (645) greater than procaterol (1440) greater than terbutaline (6420). In rat lung membranes (predominantly beta 2-subtype), the order of potency (KiL) was Iso (20.6 nM) greater than procaterol (70.2) greater than Epi (136) greater than prenalterol (412) greater than dobutamine (735) greater than or equal to Nor (744) greater than denopamine (2205) greater than terbutaline (2500). The beta 1/beta 2-selectivity as judged from the KiL/KiH values was in the order of denopamine (4.1) greater than Nor (3.3) greater than prenalterol (2.6) greater than Iso (1.5) greater than dobutamine (1.1) greater than Epi (0.55) greater than terbutaline (0.39) greater than procaterol (0.05). Practolol, a beta 1-antagonist, showed a high beta 1-selectivity (KiL/KiH = 15.3). In the presence of guanine nucleotide (GTP), the denopamine radioligand competition curve showed a rightward shift, and its Hill coefficient increased like other agonists, although the degree of the shift was less than that observed with full agonists such as Iso. These results essentially correspond with the pharmacological and biochemical properties of denopamine and confirm the beta 1-selectivity and the agonist property of this compound.
多巴胺是一种新型的口服活性强心剂。进行本实验以表征该药物对β-肾上腺素能受体亚型的结合亲和力和选择性。使用3H-二氢阿普洛尔作为放射性配体进行结合研究。多巴胺和一些β-激动剂对主要含有β1亚型的大鼠心脏膜（KiH）的结合亲和力顺序为：异丙肾上腺素（Iso，14.1 nM）＞普瑞特罗（158）＞去甲肾上腺素（Nor，227）≥肾上腺素（Epi，248）＞多巴胺（545）≥多巴酚丁胺（645）＞丙卡特罗（1440）＞特布他林（6420）。在大鼠肺膜（主要为β2亚型）中，效价顺序（KiL）为：Iso（20.6 nM）＞丙卡特罗（70.2）＞Epi（136）＞普瑞特罗（412）＞多巴酚丁胺（735）≥Nor（744）＞多巴胺（2205）＞特布他林（2500）。从KiL/KiH值判断的β1/β2选择性顺序为：多巴胺（4.1）＞Nor（3.3）＞普瑞特罗（2.6）＞Iso（1.5）＞多巴酚丁胺（1.1）＞Epi（0.55）＞特布他林（0.39）＞丙卡特罗（0.05）。β1拮抗剂心得宁表现出高β1选择性（KiL/KiH = 15.3）。在鸟嘌呤核苷酸（GTP）存在下，多巴胺放射性配体竞争曲线向右移动，其希尔系数像其他激动剂一样增加，尽管移动程度小于用Iso等完全激动剂观察到的程度。这些结果基本上与多巴胺的药理和生化特性相符，并证实了该化合物的β1选择性和激动剂特性。
