Gries J, Unger L, Einig H, Friedrich L, Hofmann H P, Kreiskott H, Lehmann H D, von Philipsborn G, Wuppermann D, Zimmermann F
Forschung und Entwicklung der Knoll AG, Ludwigshafen/Rhein.
Arzneimittelforschung. 1988 Sep;38(9):1271-9.
The present pharmacological test results characterize soquinolol (5-[3-tertiary butylamino-2-hydroxypropoxy]-2-formyl-1,2,3,4- tetrahydroisoquinoline mucate, We 704, Sertum) as a highly potent non-subtype-selective beta-adrenergic receptor blocker, which is devoid of any intrinsic sympathomimetic activity. Its localanaesthetic activity (membrane stabilizing effect) is very weak. It also shows good enteral efficacy and long duration of action. In binding studies with heart (Ki beta 1 = 3.25 nmol/l) and lung membranes (Ki beta 2 = 0.85 nmol/l) its binding profile was found to be similar to that of propranolol. Soquinolol inhibits the isoprenaline-induced tachycardia (EC50% = 48 micrograms/l) in the guinea-pig Langendorff heart in vitro to the same degree as propranolol. However, in the conscious dog soquinolol's beta 1-adrenergic blocking activity (ED 50%) on intravenous injection (5.5 micrograms/kg) and oral administration (5.8 micrograms/kg) is about twice as great as that of pindolol and 19 times (i.v.) or 138 times (p.o.) greater than that of propranolol. These results suggest 95% enteral efficacy for soquinolol (pindolol 88%, propranolol 13%). The differences in soquinolol's and propranolol's efficacy detected in vitro and in vivo are partially attributable to differences in their kinetic properties namely the lower protein binding and the higher distribution volume of soquinolol. In the conscious dog, soquinolol inhibits beta 1-(ED 50% = 4.0 micrograms/kg) and beta 2-receptors (ED 50% = 2.7 micrograms/kg) at dose levels which do not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
目前的药理学测试结果表明，索喹洛尔（5-[3-叔丁氨基-2-羟基丙氧基]-2-甲酰基-1,2,3,4-四氢异喹啉粘酸盐，We 704，Sertum）是一种高效的非亚型选择性β-肾上腺素能受体阻滞剂，无任何内在拟交感活性。其局部麻醉活性（膜稳定作用）非常弱。它还具有良好的肠内疗效和长效作用。在与心脏（Kiβ1 = 3.25 nmol/l）和肺膜（Kiβ2 = 0.85 nmol/l）的结合研究中，发现其结合特征与普萘洛尔相似。索喹洛尔在体外对豚鼠Langendorff心脏中异丙肾上腺素诱导的心动过速（EC50% = 48微克/升）的抑制程度与普萘洛尔相同。然而，在清醒犬中，索喹洛尔静脉注射（5.5微克/千克）和口服给药（5.8微克/千克）时的β1-肾上腺素能阻断活性（ED 50%）约为吲哚洛尔的两倍，是普萘洛尔静脉注射时的19倍（口服时为138倍）。这些结果表明索喹洛尔的肠内疗效为95%（吲哚洛尔为88%，普萘洛尔为13%）。在体外和体内检测到的索喹洛尔和普萘洛尔疗效差异部分归因于它们的动力学性质差异，即索喹洛尔的蛋白结合较低和分布容积较高。在清醒犬中，索喹洛尔在剂量水平上对β1-（ED 50% = 4.0微克/千克）和β2-受体（ED 50% = 2.7微克/千克）的抑制作用无显著差异。（摘要截于250字）
