Arnold J M, McDevitt D G
Br J Clin Pharmacol. 1983 Aug;16(2):175-84. doi: 10.1111/j.1365-2125.1983.tb04982.x.
Six healthy subjects were studied on two occasions. Graded bolus injections of isoprenaline sulphate were given intravenously and control dose-response curves were drawn for the changes in heart rate and blood pressure. In a random order each subject received an intravenous infusion of either propranolol or practolol and further dose-response curves were constructed PRE- and POST-atropine (0.04 mg/kg). Exercise tachycardia was reduced 26.1 +/- 2.7% by propranolol and this was not significantly different from the reduction by practolol (21.2 +/- 1.9%). Propranolol attenuated the isoprenaline tachycardia (dose ratio 43.7) and after atropinisation the dose ratio was not significantly altered (41.1). Practolol also attenuated the isoprenaline tachycardia (dose ratio 4.4) but after atropinisation the dose ratio was significantly increased to 8.8, though this remained significantly less than the dose ratio for propranolol. At a heart rate increase of 25 beats/min, the isoprenaline-induced control fall in mean blood pressure was 9-11 mm Hg. After propranolol administration this fall was converted to a small increase of + 2.3 +/- 1.3 mm Hg. Following practolol, however, the mean blood pressure reduction was 19.7 +/- 2.9 mm Hg. Practolol did not significantly block the isoprenaline-induced fall in diastolic pressure. The difference in potency of propranolol and practolol, demonstrated by their effect on isoprenaline induced tachycardia at doses shown to have equal effects on exercise tachycardia, is contributed to but not fully explained by the reflex withdrawal of cardiac vagal tone which occurs with cardioselective but not non-selective antagonists.
对6名健康受试者进行了两次研究。静脉内给予不同剂量的硫酸异丙肾上腺素推注,并绘制心率和血压变化的对照剂量反应曲线。按照随机顺序,每位受试者接受普萘洛尔或普拉洛尔的静脉输注,并在给予阿托品(0.04mg/kg)前后构建进一步的剂量反应曲线。普萘洛尔使运动性心动过速降低了26.1±2.7%,这与普拉洛尔引起的降低(21.2±1.9%)无显著差异。普萘洛尔减弱了异丙肾上腺素引起的心动过速(剂量比为43.7),阿托品化后剂量比无显著改变(41.1)。普拉洛尔也减弱了异丙肾上腺素引起的心动过速(剂量比为4.4),但阿托品化后剂量比显著增加至8.8,尽管仍显著低于普萘洛尔的剂量比。当心率增加25次/分钟时,异丙肾上腺素引起的对照平均血压下降为9 - 11mmHg。给予普萘洛尔后,这种下降转变为小幅升高,为+2.3±1.3mmHg。然而,给予普拉洛尔后,平均血压下降为19.7±2.9mmHg。普拉洛尔并未显著阻断异丙肾上腺素引起的舒张压下降。在对运动性心动过速有相同作用的剂量下,普萘洛尔和普拉洛尔对异丙肾上腺素引起心动过速的作用所显示的效价差异,部分是由于心脏迷走神经张力的反射性减退所致,这种情况发生在心脏选择性而非非选择性拮抗剂给药时,但这并不能完全解释这种差异。