Pharmacodynamics is the study of the biochemical and physiological effects of drugs and their mechanisms of action. The effects of most drugs result from their interaction with macromolecular components of the organism. The term drug receptor or drug target denotes the cellular macromolecule or macromolecular complex with which the drug interacts to elicit a cellular response. Drugs commonly alter the rate or magnitude of an intrinsic cellular response rather than create new responses. Drug receptors are often located on the surface of cells, but may also be located in specific intracellular compartments such as the nucleus.
Many drugs also interact with acceptors (e.g., serum albumin) within the body. Acceptors are entities that do not directly cause any change in biochemical or physiological response. However, interactions of drugs with acceptors can alter the pharmacokinetics of a drug's actions.
Many drug receptors are proteins that normally serve as receptors for endogenous regulatory ligands. These drug targets are termed physiological receptors. Drugs that bind to physiological receptors and mimic the regulatory effects of the endogenous signaling compounds are termed agonists. If the drug binds to the same recognition site as the endogenous agonist, the drug is said to be a primary agonist. Allosteric (or allotopic) agonists bind to a different region on the receptor referred to as an allosteric or allotopic site. Drugs that block or reduce the action of an agonist are termed antagonists. Antagonism generally results from competition with an agonist for the same or overlapping site on the receptor (a syntopic interaction), but can also occur by interacting with other sites on the receptor (allosteric antagonism), by combining with the agonist (chemical antagonism), or by functional antagonism by indirectly inhibiting the cellular or physiological effects of the agonist. Agents that are only partly as effective as agonists are termed partial agonists. Many receptors exhibit some constitutive activity in the absence of a regulatory ligand; drugs that stabilize such receptors in an inactive conformation are termed inverse agonists (Figure 3–1). In the presence of a full agonist, partial and inverse agonists will behave as competitive antagonists.
Regulation of the activity of a receptor with conformation-selective drugs. The ordinate is the activity of the receptor produced by Ra, the active receptor conformation (e.g., stimulation of adenylyl cyclase by a β adrenergic receptor). If a drug L selectively binds to Ra, it will produce a maximal response. If L has equal affinity for Ri and Ra, it will not perturb the equilibrium between them and will have no effect on net activity; L would appear as an inactive compound. If the drug selectively binds to Ri, then the net amount of Ra will be diminished. If L can bind to receptor in an active conformation Ra but also ...