BOYD H, BURNSTOCK G, CAMPBELL G, JOWETT A, O'SHEA J, WOOD M
Br J Pharmacol Chemother. 1963 Jun;20(3):418-35. doi: 10.1111/j.1476-5381.1963.tb01479.x.
The adrenergic blocking agents tolazoline, phentolamine, piperoxan, yohimbine, phenoxybenzamine, bretylium and guanethidine block the excitatory actions both of cholinergic nerves and of added acetylcholine on a variety of vertebrate smooth muscle preparations. These cholinergic blocking actions often occurred with concentrations lower than those required to block the response of the guinea-pig vas deferens to stimulation of the adrenergic hypogastric nerve. The anti-acetylcholine activities of these drugs have been studied in detail, using the guinea-pig rectum and the toad bladder as test organs. In preparations sensitive to eserine, the anticholinesterase actions of the drugs competed with their anti-acetylcholine actions, so that either potentiation or block of responses to acetylcholine and to cholinergic nerve stimulation occurred with different concentrations. The responses of the toad bladder to acetylcholine were not potentiated by eserine. This enabled the antagonism of acetylcholine by the anti-adrenergic drugs to be estimated without interference from their anticholinesterase activity. When blocking activity was assessed on guinea-pig rectum previously treated with dyflos, the results were qualitatively similar to those on the toad bladder. Phenoxybenzamine often completely blocks responses both to added acetylcholine and to cholinergic nerve stimulation in concentrations less than those required to block adrenergic nerves. Guanethidine and piperoxan also show strong cholinergic blocking activity. Bretylium, yohimbine, tolazoline and phentolamine were less potent. However, in concentrations required to block the effect on the vas deferens of hypogastric nerve stimulation, these drugs at least halved the effects of acetylcholine and often of cholinergic nerve stimulation. It is concluded that these adrenergic blocking agents cannot be used to distinguish conclusively between adrenergic and cholinergic nerves. For reliable analysis of autonomic innervation, the substances released upon nerve stimulation must be identified by specific biochemical techniques or bioassay.
肾上腺素能阻滞剂妥拉唑啉、酚妥拉明、哌罗克生、育亨宾、酚苄明、溴苄铵和胍乙啶可阻断胆碱能神经以及外加乙酰胆碱对多种脊椎动物平滑肌制剂的兴奋作用。这些胆碱能阻断作用通常在低于阻断豚鼠输精管对肾上腺素能腹下神经刺激反应所需浓度时出现。已使用豚鼠直肠和蟾蜍膀胱作为测试器官，详细研究了这些药物的抗乙酰胆碱活性。在对毒扁豆碱敏感的制剂中，药物的抗胆碱酯酶作用与其抗乙酰胆碱作用相互竞争，因此，在不同浓度下，对乙酰胆碱和胆碱能神经刺激的反应会出现增强或阻断。蟾蜍膀胱对乙酰胆碱的反应不会被毒扁豆碱增强。这使得能够在不受其抗胆碱酯酶活性干扰的情况下，评估抗肾上腺素能药物对乙酰胆碱的拮抗作用。当在预先用双氟磷处理过的豚鼠直肠上评估阻断活性时，结果在质量上与在蟾蜍膀胱上的结果相似。酚苄明通常在低于阻断肾上腺素能神经所需浓度时，就能完全阻断对外加乙酰胆碱和胆碱能神经刺激的反应。胍乙啶和哌罗克生也表现出较强的胆碱能阻断活性。溴苄铵、育亨宾、妥拉唑啉和酚妥拉明的效力较弱。然而，在阻断腹下神经刺激对输精管作用所需的浓度下，这些药物至少能使乙酰胆碱的作用减半，并且常常能使胆碱能神经刺激的作用减半。得出的结论是，这些肾上腺素能阻滞剂不能用于明确区分肾上腺素能神经和胆碱能神经。为了可靠地分析自主神经支配，必须通过特定的生化技术或生物测定法来鉴定神经刺激时释放的物质。
