功能拮抗作用作为测定豚鼠离体心房中拟交感神经胺的解离常数和相对效能的一种方法。
Functional antagonism as a means of determining dissociation constants and relative efficacies of sympathomimetic amines in guinea-pig isolated atria.
作者信息
Broadley K J, Nicholson C D
出版信息
Br J Pharmacol. 1979 Jul;66(3):397-404. doi: 10.1111/j.1476-5381.1979.tb10844.x.
1 The positive inotropic and chronotropic responses to sympathomimetic amines were examined in guinea-pig isolated atria. 2 The order of potency measured from EC50 values was isoprenaline greater than orciprenaline greater than salbutamol greater than or equal to fenoterol greater than terbutaline. Terbutaline and salbutamol were partial agonists on rate and together with orciprenaline and fenoterol also on tension responses. 3 Functional antagonism by carbachol caused a rightwards shift of the dose-response curve and depression of the maximum response. The rate maxima for orciprenaline, fenoterol and terbutaline were above that of isoprenaline. All the tension maxima were below isoprenaline. 4 Dissociation constants (KA) and relative efficacies (er) were determined by analogy with irreversible antagonism. 5 The relative orders of affinity (KA) were isoprenaline greater than orciprenaline greater than fenoterol greater than salbutamol greater than terbutaline. Affinities were identical on rate and tension. 6 The relative efficacies were all greater than isoprenaline for rate responses. On tension they were the same or less than isoprenaline. 7 The implications of these results are discussed, in particular the fact that a partial agonist has a greater efficacy than a full agonist.
1 在豚鼠离体心房中研究了对拟交感胺的正性肌力和变时反应。2 根据半数有效浓度（EC50）值测定的效价顺序为：异丙肾上腺素＞奥西那林＞沙丁胺醇≥非诺特罗＞特布他林。特布他林和沙丁胺醇对心率是部分激动剂，对张力反应而言，它们与奥西那林和非诺特罗也是部分激动剂。3 卡巴胆碱引起的功能性拮抗导致剂量 - 反应曲线右移且最大反应降低。奥西那林、非诺特罗和特布他林的心率最大值高于异丙肾上腺素。所有的张力最大值均低于异丙肾上腺素。4 解离常数（KA）和相对效能（er）通过与不可逆拮抗作用类比来确定。5 亲和力（KA）的相对顺序为：异丙肾上腺素＞奥西那林＞非诺特罗＞沙丁胺醇＞特布他林。心率和张力方面的亲和力相同。6 对于心率反应，所有相对效能均大于异丙肾上腺素。对于张力反应，它们与异丙肾上腺素相同或更低。7 讨论了这些结果的意义，特别是部分激动剂比完全激动剂具有更高效能这一事实。
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