Intrinsic activity: partial agonists and partial antagonists

Abstract

The effect of bioactive agents in many, if not most, cases should be considered as the result of an interaction among molecules of the active agent, the drug, and particular molecular sites of action, receptors (sometimes enzymes), in the biological object. In those cases in which a drug-receptor interaction is involved, two essential parameters should be distinguished, namely, the affinity of the active agent to its receptor, and the intrinsic activity of the active agent, i.e., the capacity to activate the receptors in the process of the drug-receptor interaction. Compounds that have only an affinity to particular types of receptors without an intrinsic activity will behave as blocking agents. Compounds may greatly differ in their affinity. Also, the capacity of bioactive agents to activate their specific receptors, the intrinsic activity, may differ for different compounds. These variations result in a differentiation among full agonists, partial agonists, partial antagonists, and full antagonists, which, besides, their affinity to the receptors, display a high, intermediate, low, and zero intrinsic activity, respectively, for the receptors. Examples of partial antagonists are the adrenergic blockers with intrinsic sympathomimetic activity. Various aspects of partial agonists and partial antagonists are discussed and elucidated.