Non-competitive antagonism

Non-competitive antagonism

In non-competitive antagonism a ligand (agonist) and an irreversible antagonist compete for the binding site on the receptors. However, once the irreversible antagonist has bound, the receptor remains occupied and can no longer respond to the binding of the agonist.

The graph shows the specific binding of the ligand [agonist] alone, and in presence of increasing concentrations of irreversible antagonist. In the absence of antagonist, the ligand is able to bind all the receptors

that are present (black line).

The presence of antagonist results in decrease of the maximum binding (green line): in other words, once the antagonist has bound the receptor, the agonist cannot achieve full binding anymore, no matter how high its concentration. The higher the antagonist concentration, the lower the maximal binding of the agonist (red line).

Thus, non-competitive antagonists reduce agonist maximal response (efficacy), but not its affinity.