Kenakin T P, Angus J A
J Pharmacol Exp Ther. 1981 Nov;219(2):474-80.
Both tolazoline and clonidine produce agonist effects sensitive to histamine H2-receptor antagonism in whole animals and a variety of isolated tissues. In guinea-pig right atria, tolazoline concentration-response curves were shifted to the right and progressively depressed by cimetidine. Clonidine produced a submaximal histamine-like tachycardia which was converted by cimetidine to a depression of sinus rate. Neither tolazoline nor clonidine stimulated histamine H2-receptors in rabbit right atria. Instead, these agents were very weak inhibitors of histamine with a pA2 for tolazoline of 3.3 and for clonidine of 3.7. No appreciable histamine H1-receptor activity was evident for either drug in experiments with guinea-pig ileum. The weak histamine H2-receptor affinity is inconsistent, from a quantitative point of view, with the hypothesis that the agonist activity results from direct stimulation of histamine receptors, but all data re compatible with previous evidence which suggests that these drugs release endogenous histamine.
妥拉唑啉和可乐定在全动物及多种离体组织中均可产生对组胺H2受体拮抗敏感的激动剂效应。在豚鼠右心房，西咪替丁使妥拉唑啉的浓度-反应曲线右移并逐渐压低。可乐定产生次最大组胺样心动过速，西咪替丁可将其转变为窦性心率抑制。妥拉唑啉和可乐定在兔右心房均不刺激组胺H2受体。相反，这些药物是非常弱的组胺抑制剂，妥拉唑啉的pA2为3.3，可乐定的pA2为3.7。在豚鼠回肠实验中，两种药物均未表现出明显的组胺H1受体活性。从定量角度来看，弱的组胺H2受体亲和力与激动剂活性源于直接刺激组胺受体的假说不一致，但所有数据均与先前表明这些药物释放内源性组胺的证据相符。
