Medical Pharmacology Topics
Usually drug effect is measured instead of actual receptor binding. When measuring response instead of binding, the measured Kd is an apparent dissociation constant (Kdapp), not the real Kd, although they are very close (Kdapp » Kd).
To simplify the complexity of receptor ligand interaction and ultimate effects, all processes beyond drug binding are combined into an unidentified "response" step (D).
R + L 
RL 
D
The occupancy model assumes that the magnitude of D is proportional to [RL], and maximal response is produced when all receptors are occupied:
D
µ [RL] ;
Dmax
µ [R]T
and [RL] = [L]__
[R]T
Kd + [L]
Þ D
= [RL]
= [L]__
Dmax [R]T
Kd + [L]
Therefore, occupancy of the receptor is the limiting step in determining drug action, and all the action of a drug can be ascribed to its affinity for the receptor. The occupancy model does not apply to antagonists, since they block the appropriate response of the system. ([RL] is NOT µ D since D = 0).
Efficacy is the ability of a drug to activate a receptor (LR*). The occupancy model can be expanded to include efficacy:
R + L
RL LR*
D
|------- affinity -------|
|------ efficacy -----|
This model breaks drug action into two functions: to occupy the receptor (affinity) and to activate it (efficacy). An agonist has affinity for the receptor and full efficacy. An antagonist has affinity for the receptor, but occupied receptors are inactive, i.e. the antagonist has no efficacy.
A partial agonist has affinity for the receptor but the occupied receptor produces a lesser effect than if occupied by a full agonist. The dose-response curve of a partial agonist will look like that of a competitive inhibitor.
An inverse agonist bind to receptors and hold them in fully or partially inactive states in such a way that, if there was a measurable basal (unoccupied) action of the receptor, the reverse agonist will lower that activity below the basal sta