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Construction of antagonist dose-response curves for estimation of pA2-values by Schild-plot analysis and detection of allosteric interactions.构建拮抗剂剂量反应曲线，用于通过Schild图分析估计pA2值并检测变构相互作用。
Br J Pharmacol. 1992 Jul;106(3):710-6. doi: 10.1111/j.1476-5381.1992.tb14399.x.
2
Experimental and theoretical comparisons between the classical Schild analysis and a new alternative method to evaluate the pA2 of competitive antagonists.经典希尔德分析与评估竞争性拮抗剂pA2的一种新替代方法之间的实验和理论比较。
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A new method for estimating dissociation constants of competitive and non-competitive antagonists with no prior knowledge of agonist concentrations.一种无需事先了解激动剂浓度即可估算竞争性和非竞争性拮抗剂解离常数的新方法。
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Some quantitative uses of drug antagonists.药物拮抗剂的一些定量应用。
Br J Pharmacol Chemother. 1959 Mar;14(1):48-58. doi: 10.1111/j.1476-5381.1959.tb00928.x.
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Drug antagonism and pAx.药物拮抗作用与pAx
Pharmacol Rev. 1957 Jun;9(2):242-6.
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A theoretical basis of molecular pharmacology. I. Interactions of one or two compounds with one receptor system.分子药理学的理论基础。I. 一种或两种化合物与一种受体系统的相互作用。
Arzneimittelforschung. 1956 May;6(5):282-93.
4
Differentiation between bronchodilation and universal adenosine antagonism among xanthine derivatives.黄嘌呤衍生物之间支气管扩张作用与普遍腺苷拮抗作用的差异。
Life Sci. 1982 Jun 21;30(25):2181-9. doi: 10.1016/0024-3205(82)90292-2.
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Theoretical and practical problems with the assessment of intrinsic efficacy of agonists: efficacy of reputed beta-1 selective adrenoceptor agonists for beta-2 adrenoceptors.激动剂内在效能评估的理论与实践问题：公认的β-1选择性肾上腺素能受体激动剂对β-2肾上腺素能受体的效能
J Pharmacol Exp Ther. 1982 Nov;223(2):416-23.
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Statistical quality control and routine data processing for radioimmunoassays and immunoradiometric assays.放射免疫分析和免疫放射分析的统计质量控制及常规数据处理
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7
Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.抑制常数（K1）与导致酶促反应50%抑制率（I50）的抑制剂浓度之间的关系。
Biochem Pharmacol. 1973 Dec 1;22(23):3099-108. doi: 10.1016/0006-2952(73)90196-2.
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Influence of ligand choice on the apparent binding profile of gallamine to cardiac muscarinic receptors. Identification of three main types of gallamine-muscarinic receptor interactions.配体选择对加拉明与心脏毒蕈碱受体表观结合谱的影响。加拉明与毒蕈碱受体相互作用的三种主要类型的鉴定。
J Pharmacol Exp Ther. 1988 Sep;246(3):829-38.
9
Simple pA2 estimation of partial agonists: comparison with the Kaumann-Blinks method.部分激动剂的简单pA2估计：与考曼-布林克斯方法的比较。
J Pharmacol Methods. 1988 Mar;19(1):47-56. doi: 10.1016/0160-5402(88)90044-7.
10
Gallamine allosterically antagonizes muscarinic receptor-mediated inhibition of adenylate cyclase activity in the rat myocardium.加拉明可别构性拮抗毒蕈碱受体介导的对大鼠心肌中腺苷酸环化酶活性的抑制作用。
J Pharmacol Exp Ther. 1988 Nov;247(2):596-602.

构建拮抗剂剂量反应曲线，用于通过Schild图分析估计pA2值并检测变构相互作用。

Construction of antagonist dose-response curves for estimation of pA2-values by Schild-plot analysis and detection of allosteric interactions.

作者信息

Pöch G, Brunner F, Kühberger E

机构信息

Institut für Pharmacokogie und Toxikologie, Universität Graz, Austria.

出版信息

Br J Pharmacol. 1992 Jul;106(3):710-6. doi: 10.1111/j.1476-5381.1992.tb14399.x.

DOI:10.1111/j.1476-5381.1992.tb14399.x
PMID:1504755
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1907557/
Abstract
  1. One aim of this paper is to show an alternative approach for the determination of antagonist affinity estimates, KB and pA2, by construction and evaluation of antagonist dose-response curves (DRCs), using the curve-fitting programme, ALLFIT. 2. Parallel antagonist DRCs were derived by vertical analysis of families of conventional agonist DRCs in the presence and absence of an antagonist at a certain agonist concentration above its ED50. The latter represents a chosen, i.e. fixed dose-ratio (DR). The antagonist concentration that reduces an agonist effect to its Emax/2 was termed Bx. It corresponds to B, the fixed antagonist concentration, tested to obtain DR-1, conventionally. 3. The dissociation constant was calculated as KB = Bx/DR-1, analogous to the conventional approach (KB = B/DR-1). Likewise, pA2-values were estimated by plotting log Bx, obtained by the alternative approach, vs log (DR-1) in an 'alternative Schild plot'. 4. Experimental agonist DRCs from our laboratory and from the literature were analysed and KB- and pA2-values obtained by the alternative approach were compared with those obtained by the conventional method. The results showed a very good agreement (correlation) between the pA2-values obtained by either method (slope = 1.02, r = 0.99, n = 9), in agreement with theoretical DRCs. 5. Besides estimation of KB and pA2, antagonist DRCs were also evaluated qualitatively. The most important finding was that allosteric antagonists or competitive antagonists with an allosteric component, such as gallamine, showed a significant reduction in the maximum of the antagonist DRCs (Imax). The evaluation of antagonist DRCs appears to be a sensitive procedure to detect allosteric interactions.6. This alternative approach can supplement or replace the conventional approach for the evaluation of antagonists on a quantitative and qualitative basis. The alternative approach appears of special advantage where the supply and/or the solubility of the agonist is limited, resulting in incomplete agonist DRCs.7. For rapid screening of potential antagonists, a single antagonist DRC at the maximum effective agonist concentration may be constructed to calculate KB reliably.
摘要
  1. 本文的一个目的是展示一种通过构建和评估拮抗剂剂量 - 反应曲线（DRCs）来测定拮抗剂亲和力估计值KB和pA2的替代方法，使用曲线拟合程序ALLFIT。2. 通过对在高于其ED50的特定激动剂浓度下存在和不存在拮抗剂时的常规激动剂DRC族进行垂直分析，得出平行拮抗剂DRC。后者代表一个选定的，即固定的剂量比（DR）。将使激动剂效应降低至其Emax/2的拮抗剂浓度称为Bx。它对应于传统上为获得DR - 1而测试的固定拮抗剂浓度B。3. 解离常数计算为KB = Bx/DR - 1，类似于传统方法（KB = B/DR - 1）。同样，通过在“替代的Schild图”中绘制通过替代方法获得的log Bx与log（DR - 1）来估计pA2值。4. 分析了来自我们实验室和文献的实验性激动剂DRC，并将通过替代方法获得的KB和pA2值与通过传统方法获得的值进行比较。结果表明，两种方法获得的pA2值之间具有非常好的一致性（相关性）（斜率 = 1.02，r = 0.99，n = 9），与理论DRC一致。5. 除了估计KB和pA2之外，还对拮抗剂DRC进行了定性评估。最重要的发现是变构拮抗剂或具有变构成分的竞争性拮抗剂，如加拉明，显示出拮抗剂DRC的最大值（Imax）显著降低。拮抗剂DRC的评估似乎是检测变构相互作用的一种灵敏方法。6. 这种替代方法可以在定量和定性基础上补充或取代评估拮抗剂的传统方法。在激动剂的供应和/或溶解度有限，导致激动剂DRC不完整的情况下，替代方法似乎具有特殊优势。7. 为了快速筛选潜在拮抗剂，可以构建在最大有效激动剂浓度下的单个拮抗剂DRC以可靠地计算KB。