Kenakin Terry
GlaxoSmithKline Research Institute, Research Triangle Park, North Carolina, USA.
Curr Protoc Pharmacol. 2008 Sep;Chapter 4:Unit 4.1. doi: 10.1002/0471141755.ph0401s42.
Historically, the earliest methods used to quantitatively measure the fundamental properties of drugs (namely affinity and efficacy) employed isolated tissues, and it is in this realm that the null methods used to define "receptor pharmacology" were described. This unit describes these methods and their use to specifically classify agonists (through potency ratios and determination of relative affinities and efficacies) and antagonists (through analysis of surmountable and insurmountable antagonism) to yield estimates of potency. Different drugs can yield different behaviors in various tissues, so this unit is centered on a flow diagram to indicate the type of analysis appropriate for the behavior observed. For example, some agonists may be full agonists in some tissues and partial agonists in others, while some antagonists may demonstrate surmountable simple competitive antagonism in some tissues and insurmountable non-competitive antagonism in others. Methods exist for determination of affinity and efficacy for all of these behaviors, and these are delineated in this unit.
从历史上看，最早用于定量测量药物基本特性（即亲和力和效能）的方法是使用离体组织，正是在这个领域中描述了用于定义“受体药理学”的无效方法。本单元介绍了这些方法及其用于对激动剂（通过效价比以及相对亲和力和效能的测定）和拮抗剂（通过对可克服和不可克服拮抗作用的分析）进行特定分类以得出效价估计值的用途。不同的药物在各种组织中可能会产生不同的行为，因此本单元以流程图为核心，以表明适合所观察到的行为的分析类型。例如，一些激动剂在某些组织中可能是完全激动剂，而在其他组织中可能是部分激动剂，而一些拮抗剂在某些组织中可能表现出可克服的简单竞争性拮抗作用，而在其他组织中则表现出不可克服的非竞争性拮抗作用。存在用于测定所有这些行为的亲和力和效能的方法，本单元对此进行了描述。
