Dynamics of Drug–Receptor Binding

DYNAMICS OF DRUG–RECEPTOR BINDING

The drug molecule, following its administration and passage to the area immediately adjacent to the recep-tor surface (sometimes called the biophase), must bond with the receptor before it can initiate a response. Resisting this bond formation is a random thermal agi-tation that is inherent in every molecule and tends to keep the molecule in constant motion. Under normal circumstances, the electrostatic attraction of the ionic bond, which can be exerted over longer distances than can the attraction of either the hydrogen or van der Waals bond, is the first force that draws the ionized mol-ecule toward the oppositely charged receptor surface. This is a reasonably strong bond and will lend some sta-bility to the drug–receptor complex.

Generally, the ionic bond must be reinforced by a hydrogen or van der Waals bond or both before signifi-cant receptor activation can occur. This is true because unreinforced bonds are too easily and quickly broken by the energy of thermal agitation to permit sufficient time for adequate drug–receptor interaction to take place. The better the structural congruity (i.e., fit) be-tween drug and its receptor, the more secondary (i.e., hydrogen and van der Waals) bonds can form.

Even if extensive binding has taken place, unless co-valent bond formation has occurred, the drug–receptor complex can still dissociate. Once dissociation has oc-curred, drug action is terminated. For most drug–receptor interactions, there is a continual random association and dissociation. The frequencies of association and dis-sociation are a function of the affinity between the drug and the receptor, the density of receptors, and the con-centration of drug in the biophase. The magnitude of the response is generally considered to be a function of the concentration of the drug–receptor complexes formed at any moment in time.