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某些β受体拮抗剂的抗心律失常、局部麻醉及肾上腺素能阻断活性

Anti-arrhythmic, local anaesthetic, and adrenergic blocking activity of some beta-receptor antagonists.

作者信息

Hermansen K

出版信息

Br J Pharmacol. 1969 Mar;35(3):476-86. doi: 10.1111/j.1476-5381.1969.tb08289.x.

Abstract
  1. The antagonistic effect of the beta-receptor blocking compounds propranolol, Ph QA 33 and INPEA on ouabain-induced cardiac fibrillations in guinea-pigs was compared with their local anaesthetic and beta-receptor blocking properties.2. All three compounds were found capable of increasing the tolerance to ouabain and of reversing ouabain-induced fibrillations, the ED50 being 0.3 mg/kg intravenously, 0.5 mg/kg intravenously, and 1.5 mg/kg intravenously, respectively for propranolol, Ph QA 33 and INPEA.3. Propranolol and Ph QA 33 were found to be moderate to strong local anaesthetics while INPEA had a considerably weaker though significant effect.4. The order of potency as beta-receptor blocking compounds was propranolol >/= Ph QA 33 >> INPEA, the latter compound being less than 1% as active as propranolol.5. Despite the surprising finding that INPEA was effective against non-catecholamine-induced arrhythmias, the results support the general assumption that the anti-arrhythmic effect of beta-receptor blocking compounds is related to their local anaesthetic action rather than to their beta-blocking ability.
摘要
  1. 将β受体阻断化合物普萘洛尔、Ph QA 33和INPEA对哇巴因诱导的豚鼠心脏纤颤的拮抗作用与其局部麻醉和β受体阻断特性进行了比较。

  2. 发现所有三种化合物均能提高对哇巴因的耐受性并逆转哇巴因诱导的纤颤,普萘洛尔、Ph QA 33和INPEA的静脉注射半数有效量(ED50)分别为0.3mg/kg、0.5mg/kg和1.5mg/kg。

  3. 发现普萘洛尔和Ph QA 33为中度至强效局部麻醉剂,而INPEA的作用虽明显较弱但仍有显著效果。

  4. 作为β受体阻断化合物的效力顺序为普萘洛尔≥Ph QA 33 >> INPEA,后一种化合物的活性不及普萘洛尔的1%。

  5. 尽管发现INPEA对非儿茶酚胺诱导的心律失常有效这一结果令人惊讶,但这些结果支持了一个普遍的假设,即β受体阻断化合物的抗心律失常作用与其局部麻醉作用有关,而非与其β阻断能力有关。

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Surface tension effects of beta-adrenergic blocking drugs.β-肾上腺素能阻滞剂的表面张力效应。
J Pharm Pharmacol. 1968 Oct;20(10):813-5. doi: 10.1111/j.2042-7158.1968.tb09652.x.
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The reversal of phenoxybenzamine-produced alpha-adrenoceptor blockade by the isomers of propranolol and INPEA.
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本文引用的文献

5
[Problem of standardization tests for local anesthetics].
Arzneimittelforschung. 1958 Mar;8(3):137-41.
6
A simple new quantitative method for testing local anaesthetics.一种用于测试局部麻醉剂的简单新型定量方法。
Br J Pharmacol Chemother. 1956 Jun;11(2):104-6. doi: 10.1111/j.1476-5381.1956.tb01036.x.
7
Optical isomers of propranolol.普萘洛尔的光学异构体。
Nature. 1966 Jun 25;210(5043):1336-8. doi: 10.1038/2101336a0.
10
Mode of action of beta receptor antagonists on cardiac muscle.
Am J Cardiol. 1966 Sep;18(3):399-405. doi: 10.1016/0002-9149(66)90062-2.

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