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布辛多洛尔在人类心肌中表现出内在的同情作用
Peter Andreka1, Nambi Aiyar, Leslie C Olson
1Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL 33101, USA.
Circulation
|May 22, 2002
概括
布辛多洛尔 (Bucindolol) 是一种β受体阻断剂,与其他β阻断剂不同,它在人心组织中出乎意料地显示出部分激动剂活性. 这一发现可能解释了它在心力衰竭临床试验中的失败.
科学领域:
- 心脏病学 心脏病学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- β-上腺素受体抗剂是心力衰竭的标准治疗方法.
- 布辛多洛尔 (Bucindolol) 是一种非选择性β-阻断剂,在最近的一项心力衰竭试验中未能改善存活率.
- 布辛多洛尔在人类心肌中的激动活性仍然存在争议.
研究的目的:
- 为了研究布辛多洛尔在人类心肌中潜在的部分激素活性.
- 为了比较布辛多洛尔的cAMP积累效应与人类心脏组织中已知的激动剂和对抗剂.
主要方法:
- 人类和老鼠的心肌带被培养并保持活力.
- 组织条纹暴露于各种β-上腺素药物 (激动剂和对抗剂).
- 测量循环腺单酸盐 (cAMP) 积累,以评估β-上腺素活性.
主要成果:
- 异二醇是一种完全的激动剂,在老鼠和人类组织中显著增加了cAMP水平.
- 卡维迪洛尔和普拉诺洛尔没有影响,而美托普罗罗尔则降低了基底cAMP.
- 然而,布辛多洛尔和沙莫特罗尔在人心肌中增加了cAMP水平,这取决于剂量.
结论:
- 布辛多洛尔在正常的人类心肌组织中表现出部分β-上腺素激动剂活性.
- 这种活性大约是Xamoterol观察到的60%的活性.
- 布辛多洛的部分激动作用可能导致其在心力衰竭中缺乏有效性.
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