MacGregor D A, Prielipp R C, Butterworth J F, James R L, Royster R L
Department of Anesthesia, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1009, USA.
Chest. 1996 Jan;109(1):194-200. doi: 10.1378/chest.109.1.194.
Dopexamine and dobutamine are traditionally described as having primarily beta 2-adrenergic agonist properties; norepinephrine is generally classified as beta 1-selective; and epinephrine, isoproterenol, and dopamine are considered mixed beta 1- and beta 2-receptor agonists. Much of this selectivity is designated from studies conducted with intact cardiovascular systems in which indirect actions (eg, norepinephrine release from presynaptic nerve terminals) are not separated from direct agonist-receptor interactions.
To assess the relative efficacy and potency of dopamine, dobutamine, dopexamine, epinephrine, isoproterenol, and norepinephrine for directly stimulating cyclic adenosine monophosphate (cAMP) production in human lymphocytes, a model of beta 2-adrenoceptor function.
Open-label, prospective paired studies of lymphocytes from nine healthy human volunteers (seven men).
Experimental laboratory of a large, university-affiliated medical center.
Concentration-response curves were generated for each adrenergic agonist; maximal cAMP production was used to compare efficacy. For the agonists that more than doubled basal cAMP concentrations, EC50 calculations were used to compare potency.
Isoproterenol and epinephrine produced the greatest concentrations of cAMP of the agonists tested. cAMP production was increased by isoproterenol at concentrations 1/10 to 1/10,000 that of the other agonists. Norepinephrine stimulated cAMP production only one third as much as epinephrine and isoproterenol, but more than double the level of dopamine, dobutamine, and dopexamine. EC50 concentrations for norepinephrine were 10-fold higher than epinephrine and 50-fold higher than isoproterenol.
Epinephrine and isoproterenol are the most efficacious and potent direct-acting beta 2-adrenergic receptor agonists using this lymphocyte cAMP model. Norepinephrine exhibits significant effects on the beta-receptors on lymphocytes, suggesting beta 2-adrenoceptor effects with high concentrations of this drug. The very low cAMP levels generated by dopamine, dobutamine, and dopexamine (even in high concentrations) support other evidence that these agents have little direct effect on the beta 2-adrenoceptor.
传统上认为多培沙明和多巴酚丁胺主要具有β2 - 肾上腺素能激动剂特性；去甲肾上腺素一般归类为β1选择性；肾上腺素、异丙肾上腺素和多巴胺被视为β1和β2受体混合激动剂。这种选择性大多来自于在完整心血管系统中进行的研究，其中间接作用（如突触前神经末梢释放去甲肾上腺素）未与直接激动剂 - 受体相互作用区分开来。
评估多巴胺、多巴酚丁胺、多培沙明、肾上腺素、异丙肾上腺素和去甲肾上腺素在直接刺激人淋巴细胞中环磷酸腺苷（cAMP）生成方面的相对疗效和效价，人淋巴细胞是β2 - 肾上腺素能受体功能的一种模型。
对9名健康人类志愿者（7名男性）的淋巴细胞进行开放标签、前瞻性配对研究。
一所大型大学附属医学中心的实验实验室。
为每种肾上腺素能激动剂生成浓度 - 反应曲线；使用最大cAMP生成量来比较疗效。对于使基础cAMP浓度增加一倍以上的激动剂，使用半数有效浓度（EC50）计算来比较效价。
在所测试的激动剂中，异丙肾上腺素和肾上腺素产生的cAMP浓度最高。异丙肾上腺素在浓度为其他激动剂的1/10至1/10000时即可增加cAMP生成。去甲肾上腺素刺激cAMP生成的量仅为肾上腺素和异丙肾上腺素的三分之一，但比多巴胺、多巴酚丁胺和多培沙明的水平高出一倍多。去甲肾上腺素的EC50浓度比肾上腺素高十倍，比异丙肾上腺素高五十倍。
使用这种淋巴细胞cAMP模型，肾上腺素和异丙肾上腺素是最有效和效价最高的直接作用β2 - 肾上腺素能受体激动剂。去甲肾上腺素对淋巴细胞上的β受体有显著作用，提示高浓度时该药具有β2 - 肾上腺素能受体效应。多巴胺、多巴酚丁胺和多培沙明（即使在高浓度时）产生的cAMP水平非常低，这支持了其他证据，即这些药物对β2 - 肾上腺素能受体几乎没有直接作用。
