PHARMACOLOGY OF 4-HYDROXYPROPRANOLOL, A METABOLITE OF PROPRANOLOL
PHARMACOLOGY OF 4-HYDROXYPROPRANOLOL, A METABOLITE OF PROPRANOLOL
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DOI：
10.1111/j.1476-5381.1971.tb07171.x
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发表时间：
1971-01-01
影响因子：
7.3
通讯作者：
ODONNELL, SR
中科院分区：
文献类型：
--
作者：
FITZ GERALD, JD;ODONNELL, SR
14-羟基普萘洛尔是普萘洛尔口服给药后产生的代谢产物，已被证明是一种β-肾上腺素受体阻滞剂。在拮抗异丙肾上腺素对猫心率和血压的影响以及拮抗异丙肾上腺素对豚鼠支气管痉挛的保护作用方面，其效力与普萘洛尔相似。它不是心脏选择性的。2在缺乏儿茶酚胺的大鼠中，4-羟基普萘洛尔引起心率增加，表明它具有内在的拟交感神经活性。3在麻醉犬中，4-羟基普萘洛尔在0·09-1·25 mg/kg的剂量范围内引起心率和dP/dt降低，A-V传导时间增加。这些效应是β肾上腺素受体阻滞的结果。在缺乏儿茶酚胺的犬中，这些相同剂量可导致心率和dP/dt增加以及A-V传导时间缩短。这些反应被普萘洛尔拮抗，并且是由于化合物的内在拟交感神经活性。在较高剂量（5·25和13·25 mg/kg）下，心率和dP/dt进一步呈剂量依赖性降低，A-V传导时间增加。这种趋势也见于缺乏儿茶酚胺的动物。这些变化代表了4-羟基普萘洛尔的膜稳定活性。44-羟基普萘洛尔是一种强效β-肾上腺素受体阻滞剂，具有内在拟交感神经活性和膜稳定活性。
14‐Hydroxypropranolol, a metabolite produced after oral administration of propranolol, has been shown to be a β‐adrenoceptor blocking drug. It is of similar potency to propranolol in antagonizing the effects of isoprenaline on heart rate and blood pressure in cats and against isoprenaline protection of guinea‐pigs from bronchospasm. It is not cardioselective.2In rats depleted of catecholamine 4‐hydroxypropranolol produced an increase in heart rate, suggesting that it has intrinsic sympathomimetic activity.3In anaesthetized dogs 4‐hydroxypropranolol produced a decrease in heart rate anddP/dtand an increase in A‐V conduction time at doses within the range 0·09–1·25 mg/kg. These effects are a result of β‐adrenoceptor blockade. In dogs depleted of catecholamines these same doses produced an increase in heart rate anddP/dtand a decrease in A‐V conduction time. These responses were antagonized by propranolol, and were due to the intrinsic sympathomimetic activity of the compound. At higher doses (5·25 and 13·25 mg/kg) a further dose dependent decrease in heart rate anddP/dtand an increase in A‐V conduction time occurred. This trend was also seen in animals depleted of catecholamines. These changes represent membrane stabilizing activity of 4‐hydroxypropranolol.44‐Hydroxypropranolol is a potent β‐adrenoceptor blocking drug with both intrinsic sympathomimetic activity and membrane stabilizing activity.