Kenakin T
Division of Pharmacology, Glaxo Inc., Research Triangle Park, North Carolina.
Drugs. 1990 Nov;40(5):666-87. doi: 10.2165/00003495-199040050-00003.
This paper reviews the theoretical concepts and methods utilised with isolated tissues to characterise drugs and drug receptors. Specifically the impact, on the in vitro measurement of agonist affinity and relative efficacy, of the idea that receptors bind to transduction proteins in the lipid bilayer of the cell membrane is discussed. The effects of ternary complex formation of agonist-receptor equilibria raise theoretical objections to the measurement of agonist receptor equilibrium dissociation constants. Possible 'promiscuity' of receptors with respect to the G-proteins with which they can interact makes classification of receptors by agonists suspect. The use of Schild analysis for the measurement of antagonist affinity and subsequent classification of receptors is considered in the light of recent data showing that estimates calculated with this method are heterogeneous. Resultant analysis for the detection of allosteric effects is also discussed. Lastly, the impact of molecular biology on the drug and drug receptor classification process is considered, as well as the effects of pathological processes on drug action at the receptor level.
本文综述了用于离体组织以表征药物和药物受体的理论概念和方法。具体讨论了细胞膜脂质双层中受体与转导蛋白结合这一观点对激动剂亲和力和相对效能的体外测量的影响。激动剂 - 受体平衡的三元复合物形成的影响对激动剂受体平衡解离常数的测量提出了理论质疑。受体与其可相互作用的G蛋白之间可能存在的“混杂性”使得通过激动剂对受体进行分类变得可疑。鉴于最近的数据表明用这种方法计算的估计值具有异质性，考虑了使用Schild分析来测量拮抗剂亲和力以及随后对受体进行分类的情况。还讨论了用于检测变构效应的结果分析。最后，考虑了分子生物学对药物和药物受体分类过程的影响，以及病理过程对受体水平药物作用的影响。
