Grabowski W, Lüttgau H C, Schulze J J
Br J Pharmacol. 1978 Jul;63(3):427-34. doi: 10.1111/j.1476-5381.1978.tb07794.x.
1 In spontaneously active Purkinje fibres of young cows the dose-response curves of the action of isoprenaline upon different electrophysiological parameters were measured.2 The increase in slope of diastolic depolarization could roughly be described by a one-for-one binding curve with a half maximum effect near 10(-8) M and the increase in the height of the plateau level by a two-for-one binding curve with a half maximum effect near 10(-7) M (-)-isoprenaline.3 These dose-response curves were similar to those of two parameters measured under voltage clamp conditions by other authors. The increase in slope of diastolic depolarization behaved like the shift of the activation curve for the pacemaker potassium current towards positive potentials and the growth in plateau height like the increase in the slow inward current mainly carried by Ca ions. From this conformity we propose that the parameters evaluated by us from action potential records could be used for a qualitative analysis of the action of catecholamines on pacemaker potassium current and Ca influx.4 The effects of the isomers of a new drug, 1-isopropylamino-3(4'hydroxyphenoxy)-propan-2-ol (IHP), were evaluated in the same way as those of isoprenaline. The (-)-isomer was at optimal concentrations (10(-5) M) nearly half as effective as isoprenaline in increasing frequency and slope of diastolic depolarization but caused no increase in plateau height. An identical relationship, but at 5 to 10 times higher concentrations, was obtained with the (+)-isomer.5 When 10(-4) M(-)-IHP was added to a preparation equilibrated with a maximum dose of (-)-isoprenaline (10(-6) M), frequency and plateau height declined. This result together with the observation that the effects of IHP could be blocked by the specific beta-antagonist propranolol, revealed the beta-agonistic nature of the new drug. Its inefficiency in increasing the plateau height and thus the slow (Ca) inward current was explained by its relatively low potency and intrinsic activity.
在幼年奶牛的自发活动浦肯野纤维中，测量了异丙肾上腺素作用于不同电生理参数的剂量-反应曲线。
舒张期去极化斜率的增加大致可用一对一结合曲线描述，在10(-8)M附近出现半数最大效应，而平台期水平高度的增加可用二对一结合曲线描述，在10(-7)M(-)-异丙肾上腺素附近出现半数最大效应。
这些剂量-反应曲线与其他作者在电压钳条件下测量的两个参数的曲线相似。舒张期去极化斜率的增加类似于起搏钾电流激活曲线向正电位的移动，而平台期高度的增加类似于主要由钙离子携带的缓慢内向电流的增加。基于这种一致性，我们提出，我们从动作电位记录中评估的参数可用于定性分析儿茶酚胺对起搏钾电流和钙内流的作用。
一种新药1-异丙基氨基-3(4'-羟基苯氧基)-丙-2-醇(IHP)异构体的作用，以与异丙肾上腺素相同的方式进行评估。(-)-异构体在最佳浓度(10(-5)M)下，在增加舒张期去极化频率和斜率方面的效力几乎是异丙肾上腺素的一半，但不会导致平台期高度增加。(+)-异构体在5至10倍高的浓度下得到相同的关系。
当将10(-4)M(-)-IHP添加到用最大剂量(-)-异丙肾上腺素(10(-6)M)平衡的制剂中时，频率和平台期高度下降。这一结果连同IHP的作用可被特异性β拮抗剂普萘洛尔阻断的观察结果，揭示了这种新药的β激动剂性质。其在增加平台期高度从而增加缓慢（钙）内向电流方面的无效性，是由于其相对较低的效力和内在活性所致。
