The first step in initiating a drug-induced effect is the formation of a complex between a drug and a cell component generally known as the drug receptor. Drug receptors are cellular macromolecules (Figure 1). They may be metabolic or regulatory enzymes or co-enzymes; proteins or glycoproteins associated with transport mechanisms; and structural and functional components of lipid membranes or nucleic acids.
Drugs bind to receptors by covalent, ionic, hydrogen, hydrophobic, and Van der Waals forces (Figure 2). It is of note, however, that not all drugs interact with specific receptors. Some form chemical bonds with small molecules, chelating agents, or metallic cations; others act by still obscure physiochemical mechanisms. Most drug-receptor bonds are weak, allowing the drug to disassociate from its receptor as a function of the drug’s concentration at the receptor site.
To form a drug-receptor bond, the drug must have affinity for the receptor. A drug’s affinity to a particular receptor and the type of bond formed is related to the drug’s chemical structure. Affinity is expressed as the dissociation constant or Kd of the drug, i.e., the concentration of a drug required to achieve 50 percent occupancy of its receptors. The molecular events that follow drug-receptor interactions reflect the drug’s mechanisms of action.