receptor occupancy
Receptor occupancy is simply the share of a target's receptors that currently have a drug molecule sitting in them — like counting how many seats in a theatre are filled at a given moment.
Occupancy rises as drug concentration rises and as affinity increases; at a concentration equal to the drug's Kd, half the receptors are occupied. In the simplest occupancy theory, the effect is proportional to the fraction of receptors bound, so full occupancy would give the maximum effect. Reality is often more complex, because the link between binding and response is not always one-to-one.
A key wrinkle is receptor reserve, or spare receptors: many tissues reach their maximal response while only a fraction of receptors are occupied, so 100% occupancy is not needed for 100% effect. Imaging techniques such as PET can now measure occupancy in living patients, helping match drug doses to the level of target engagement needed for benefit.
PET studies show many antipsychotics need to occupy roughly 65 to 80% of brain dopamine D2 receptors for benefit, with movement side effects rising above about 80%.
Fraction of receptors bound.
Because of spare receptors, occupancy and response are not always proportional: a drug can occupy only 20% of receptors yet still produce a near-maximal effect.