Kenakin T P
J Pharmacol Exp Ther. 1981 Feb;216(2):210-9.
In rat anococcygeus muscle, dobutamine produced concentration-related submaximal contractions which were antagonized competitively by phentolamine (pKB = 8.3) and dobutamine antagonized norepinephrine-induced contractions in a competitive manner with an equilibrium dissociation constant for the alpha adrenoceptor of 20 nM (pKB = 7.7). Therefore, dobutamine satisfied criteria for a partial agonist of alpha adrenoceptors having an affinity for alpha adrenoceptors 25 times that of norepinephrine (pKA = 6.3) in this tissue. An estimate of the relative efficacy of dobutamine showed one-fortieth the the efficacy of norepinephrine at the alpha adrenoceptors. Dobutamine contracted rabbit aorta and produced concentration-related relaxations at 1000 times greater concentrations after alkylation of alpha adrenoceptors by phenoxybenzamine. In noncontracted canine saphenous vein, dobutamine had no visible agonist activity but did produce contractions after propranolol. In partially contracted saphenous vein, dobutamine produced a small contraction which was converted to a propranolol-sensitive relaxation of tone after phentolamine. Dobutamine was a full beta adrenoceptor agonist in guinea-pig trachea under spontaneous tone but a partial agonist after strong contraction by bethanechol. This allowed measurement of the pKB of dobutamine at beta adrenoceptors (pKB = 5.35) and estimation of efficacy at beta adrenoceptors relative to isoproterenol (eDob/eIso = 1/20). No evidence for beta adrenoceptor selectivity was found in studies of potency ratios and relative efficacy using isoproterenol for comparison. Dobutamine showed a slight (2-fold) selectivity for inotropy in vitro when compared to isoproterenol in guinea-pig right and left atria. This selectivity was removed by phentolamine suggesting a cardiac alpha-like adrenoceptor effect; this finding was confirmed in propranolol-treated guinea-pig left atria. These results are discussed in terms of the in vivo effects of dobutamine and its use as a tool for classification of beta adrenoceptors, particularly the putative presynaptic beta adrenoceptor.
在大鼠肛门尾骨肌中，多巴酚丁胺产生浓度相关的次最大收缩，酚妥拉明可竞争性拮抗该收缩（pKB = 8.3），且多巴酚丁胺以竞争性方式拮抗去甲肾上腺素诱导的收缩，其对α肾上腺素受体的平衡解离常数为20 nM（pKB = 7.7）。因此，在该组织中，多巴酚丁胺符合α肾上腺素受体部分激动剂的标准，其对α肾上腺素受体的亲和力是去甲肾上腺素的25倍（pKA = 6.3）。对多巴酚丁胺相对效能的估计显示，其在α肾上腺素受体处的效能为去甲肾上腺素的四十分之一。在用苯氧苄胺使α肾上腺素受体烷基化后，多巴酚丁胺使兔主动脉收缩，并在浓度高1000倍时产生浓度相关的舒张。在未收缩的犬隐静脉中，多巴酚丁胺没有明显的激动剂活性，但在给予普萘洛尔后会产生收缩。在部分收缩的隐静脉中，多巴酚丁胺产生小的收缩，在给予酚妥拉明后转变为对普萘洛尔敏感的张力舒张。在豚鼠气管处于自主张力状态下，多巴酚丁胺是β肾上腺素受体的完全激动剂，但在被氨甲酰甲胆碱强烈收缩后则为部分激动剂。这使得能够测定多巴酚丁胺在β肾上腺素受体处的pKB（pKB = 5.35），并估计其在β肾上腺素受体处相对于异丙肾上腺素的效能（eDob/eIso = 1/20）。在使用异丙肾上腺素进行比较的效能比和相对效能研究中，未发现β肾上腺素受体选择性的证据。与豚鼠左右心房中的异丙肾上腺素相比，多巴酚丁胺在体外对心肌收缩力表现出轻微（2倍）的选择性。酚妥拉明可消除这种选择性，提示存在心脏α样肾上腺素受体效应；这一发现在用普萘洛尔处理的豚鼠左心房中得到证实。将根据多巴酚丁胺的体内效应及其作为β肾上腺素受体分类工具的用途，尤其是假定的突触前β肾上腺素受体，对这些结果进行讨论。
