| An agonist is a drug that binds to receptors and thereby alters (stabilizes) the proportion of receptors that are in the active conformation, resulting in a biologic response. A full agonist results in a maximal response by occupying all or a fraction of receptors. A partial agonist results in less than a maximal response even when the drug occupies all of the receptors. A partial agonist produces an effect if no full agonist is present, but acts as an antagonist in
the presence of a full agonist. Concentration-effect curves of partial agonists resemble curves of full agonists in the presence of a noncompetitive antagonist. |
| An antagonist is a drug that blocks the response produced by an agonist. It interacts with the receptor or other component of the effector mechanism, but is devoid of intrinsic activity (ie, the ability to elicit a response upon binding to a receptor). A competitive antagonist results in reversible inhibition that can be overcome by increasing the concentration of agonist. The presence of a competitive antagonist causes a parallel shift of the log dose-effect curve to
the right, without altering the Emax or EC50 of the agonist. A noncompetitive antagonist results in irreversible inhibition that generally prevents the agonist from producing a maximal effect (ie, Emax and EC50 are lowered). However, at low concentrations, a noncompetitive antagonist may cause a parallel shift of the log dose-effect curve to the right without reducing the maximal response of
the agonist. |
| Agonists, but not antagonists, elicit an effect even when they bind to the same site on the same receptor. An explanation is provided by both structural and functional studies, which indicate that receptors exist in at least 2 conformations, active and inactive, and these are in equilibrium. Because agonists have a higher affinity for the receptor’s active conformation, agonists drive the equilibrium to the active state, thereby activating the receptor. Conversely, antagonists have
a higher affinity for the receptor’s inactive conformation and push the equilibrium to the inactive state, producing no effect. |
| The concept of spare receptors is implicit in the definition of a noncompetitive antagonist; the latter effectively removes receptors irreversibly from the system. Yet low concentrations of a noncompetitive antagonist may result in a parallel shift of the log dose-effect curve to the right without reducing the maximal response of the agonist. This observation is attributed to a maximum response being elicited without all receptors being occupied, in which case the
tissue is said to possess spare receptors. From a functional perspective, spare receptors are significant because they increase both the sensitivity and speed of a tissue’s responsiveness to a ligand. |
