Schliep H J, Harting J
J Cardiovasc Pharmacol. 1984 Nov-Dec;6(6):1156-60.
The beta-adrenoceptor activity of the newly synthesized antagonist bisoprolol [+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol, hemifumarate), has been compared with the effect of several reference compounds in anesthetized dogs and guinea pigs. In anesthetized, bivagotomized dogs, isoprenaline dose-response relations for increase in heart rate and decrease in diastolic blood pressure were established. Bisoprolol had the largest beta 1/beta 2 ratio, i.e., 147 (102-292). Practolol showed a beta 1/beta 2 ratio greater than 17; betaxolol 6-15; acebutolol, atenolol, and metoprolol 1.1-3.2; mepindolol 0.6-1 and propranolol 0.2. In artificially ventilated guinea pigs, the activity of bisoprolol on histamine-induced increase in tracheal lateral pressure (TLP) and basal heart rate (HR) was tested: using doses taken at TLP (30 mm Hg) and HR (250 beats/min), bisoprolol exhibited the most pronounced ratio TLP/HR of 124 +/- 59, followed by atenolol 33 +/- 23, metoprolol 25 +/- 15, betaxolol 12 +/- 4, propranolol 1 +/- 0.3, and celiprolol 0.23 +/- 0.19. These experiments indicate that bisoprolol possesses a pronounced beta 1-selectivity, which seems to be superior to that of known beta 1-selective antagonists.
已将新合成的拮抗剂比索洛尔[（±）-1-[4-(2-异丙氧基乙氧基甲基)-苯氧基]-3-异丙氨基-2-丙醇，半富马酸盐]的β-肾上腺素能受体活性与几种参比化合物在麻醉犬和豚鼠中的作用进行了比较。在麻醉、双侧迷走神经切断的犬中，建立了异丙肾上腺素使心率增加和舒张压降低的剂量-反应关系。比索洛尔的β1/β2比值最大，即147（102 - 292）。心得宁的β1/β2比值大于17；倍他洛尔为6 - 15；醋丁洛尔、阿替洛尔和美托洛尔为1.1 - 3.2；甲吲洛尔为0.6 - 1；普萘洛尔为0.2。在人工通气的豚鼠中，测试了比索洛尔对组胺诱导的气管侧压（TLP）升高和基础心率（HR）的活性：使用在TLP（30 mmHg）和HR（250次/分钟）时的剂量，比索洛尔表现出最显著的TLP/HR比值，为124±59，其次是阿替洛尔33±23、美托洛尔25±15、倍他洛尔12±4、普萘洛尔1±0.3和塞利洛尔0.23±0.19。这些实验表明比索洛尔具有显著的β1选择性，这似乎优于已知的β1选择性拮抗剂。
