receptor occupancy
Receptor occupancy is simply the fraction of a target's binding sites that a drug has filled at a given concentration — like asking what proportion of parking spaces in a lot are taken. It rises from zero toward 100% as drug concentration climbs.
At equilibrium, occupancy follows a saturating curve set by affinity: at a free drug concentration equal to the Kd, occupancy is 50%; at ten times Kd it is about 91%, and at a hundred times Kd about 99%. This means the last stretch toward full occupancy is expensive — large concentration increases yield only small occupancy gains.
Occupancy is a central bridge between dose and effect, and is measured in living systems with techniques like PET imaging to confirm a drug is actually engaging its target. But occupancy alone does not predict response: receptor reserve can mean a strong effect at modest occupancy, while for some targets durable occupancy over time matters more than the peak, linking back to residence time.
For many antipsychotics, clinical benefit tends to appear once dopamine D2 receptor occupancy reaches roughly 65–70%, while occupancy above about 80% sharply raises the risk of motor side effects.
Occupancy links drug concentration to the degree of target engagement.
High occupancy does not guarantee a large effect, and full effect does not always need full occupancy — receptor reserve and signal amplification break the simple one-to-one link.