1. Full agonists The “agonists” referred to so far are FULL AGONISTS
Able to produce a maximum response for the tissue
Even though only a fraction of the receptors are occupied

2. Curve for a full agonist
100 75
% Maximum response
Typical curve
for a full agonist 50 25
0.001
0.01
0.1 1 10
100
log conc (µM)

3. Curves for Full agonist and Partial agonist
100 75
% Maximum response
PARTIAL 50 25
0.001
0.01
0.1 1 10
100
log conc (µM)

4. Relationship between occupancy and response
FULL
100 80 60
PARTIAL
Response (% maximum) 40 20
ANTAGONIST
0.0
0.2
0.4
0.6
0.8
1.0
Fractional occupancy

5. Differences between Full and Partial agonists
FULL agonist - produces maximum response even when only a FRACTION of receptors are occupied
PARTIAL agonist - CANNOT produce a maximum tissue response even when ALL receptors are occupied
Note the curves are not parallel

6. Why is there a difference?
The reason is due to EFFICACY
Full agonists are said to have a higher efficacy than partial agonists
What is efficacy?
The ability of the drug-receptor complex to produce a response
In other words how well a drug produces an effect - IN A PARTICULAR SYSTEM
i.e. can vary tissue to tissue - even when the RECEPTORS are the SAME

7. Mathematical explanation
Response depends upon
characteristics of the TISSUE
characteristics of the DRUG
Response = ƒ Ntot XA
XA + Kd
ƒ (transducer function)
Ntot (number of receptors)
Kd (dissociation constant)
 (intrinsic efficacy) ( ) }
Properties
of the TISSUE }
Properties
of the DRUG

8. Inverse agonists Do not confuse with an antagonist!!!
Receptors can exist in 2 conformational states –”2 state model”
These are “resting” and “activated”
Agonists, antagonists and inverse agonists have differing binding affinities to these states

9. Two-state model R R* Inverse agonist Agonist resting activated
RESP
resting
activated
Antagonist

10. Recommended Reading Agonists
Medical Pharmacology at a Glance, 5th Ed: Page 11
Pharmacology, 5th Ed: Pages 11-14
Basic and Clinical Pharmacology Online Book: Section I, Chapter 2, Relation between drug concentration and response, Partial Agonists