Allan G, Cambridge D, Hardy G W, Follenfant M J
Br J Pharmacol. 1987 Mar;90(3):609-15. doi: 10.1111/j.1476-5381.1987.tb11212.x.
BW A575C (N-(1-(S)-carboxy-5-[4(3-isopropylamino-2-(R, S)-hydroxypropoxy)indole-2- carboxamido]pentyl)-(R, S)-alanyl-(S)-proline) is a chemically novel agent which exhibits in a single molecule both angiotensin converting enzyme (ACE) inhibition and beta-adrenoceptor-blocking properties. BW A575C produced a competitive blockade of heart rate responses to isoprenaline in a guinea-pig right atrial preparation (pKB 7.18 +/- 0.05, cf. pindolol 8.9 +/- 0.7). BW A575C inhibited a partially purified preparation of ACE obtained from rabbit lung (IC50 10.7 +/- 2.1 nM, cf. enalaprilat, 4.4 +/- 0.8 nM). Intravenous administration of BW A575C (1-100 micrograms kg-1 min-1) to the pithed rat inhibited in a dose-dependent fashion both angiotensin I-induced pressor responses and isoprenaline-induced tachycardia. Dose-ratios obtained from such studies demonstrated that, in this preparation, BW A575C was approximately 100 times more active as an ACE inhibitor than as a beta-adrenoceptor blocking agent. Intravenous administration of BW A575C (1 mg kg-1) to the conscious rat inhibited angiotensin I-induced pressor responses, being approximately equipotent to enalapril and 10 times more potent than captopril. At the same dose, BW A575C had a similar duration of action as an ACE inhibitor to enalapril. Intravenous administration of BW A575C (1 mg kg-1) to either conscious dogs or rats inhibited both angiotensin I-induced pressor responses and isoprenaline-induced heart rate responses. Dose-ratios obtained from such studies demonstrated that in these species, BW A575C was 2-10 times more active as an ACE inhibitor than as a beta-adrenoceptor blocking agent.
BW A575C（N-(1-(S)-羧基-5-[4(3-异丙基氨基-2-(R,S)-羟基丙氧基)吲哚-2-羧酰胺基]戊基)-(R,S)-丙氨酰-(S)-脯氨酸）是一种化学结构新颖的药物，它在单个分子中同时具有血管紧张素转换酶（ACE）抑制和β-肾上腺素能受体阻断特性。在豚鼠右心房制备物中，BW A575C对异丙肾上腺素引起的心率反应产生竞争性阻断（pKB 7.18±0.05，对比吲哚洛尔为8.9±0.7）。BW A575C抑制了从兔肺中获得的部分纯化的ACE制剂（IC50 10.7±2.1 nM，对比依那普利拉为4.4±0.8 nM）。向脊髓损毁大鼠静脉注射BW A575C（1 - 100微克·千克-1·分钟-1）以剂量依赖性方式抑制了血管紧张素I引起的升压反应和异丙肾上腺素引起的心动过速。从这些研究中获得的剂量比表明，在该制备物中，BW A575C作为ACE抑制剂的活性比作为β-肾上腺素能受体阻断剂高约100倍。向清醒大鼠静脉注射BW A575C（1毫克·千克-1）抑制了血管紧张素I引起的升压反应，其效力与依那普利大致相当，比卡托普利强10倍。在相同剂量下，BW A575C作为ACE抑制剂的作用持续时间与依那普利相似。向清醒犬或大鼠静脉注射BW A575C（1毫克·千克-1）抑制了血管紧张素I引起的升压反应和异丙肾上腺素引起的心率反应。从这些研究中获得的剂量比表明，在这些物种中，BW A575C作为ACE抑制剂的活性比作为β-肾上腺素能受体阻断剂高2至10倍。
