1. ANTAGONISTS
Antagonists are substances which block the action of agonists
There are a number of types
COMPETITIVE
NON-COMPETITIVE
PARTIAL AGONISTS
PHYSIOLOGICAL
CHEMICAL
PHARMACOKINETIC

2. Typical curve for an agonist
Guinea pig ileum - carbachol log concentration response
150
100
Response (mm) 50 -2 -1 1 2 3 4
Log conc carbachol (µM)

3. Typical curve for agonist plus antagonist
Effect of atropine on carbachol log concentration response
CARB
+ ATR 10-7 M
150
100
Response (mm) 50 -2 -1 1 2 3 4
Log conc carbachol (µM)

4. Typical curve for agonist plus antagonist II
Effect of atropine on carbachol log concentration response
+ ATR
10-7 M
CARB
150
+ ATR
10-6 M
100
Response (mm) 50 -2 -1 1 2 3 4
Log conc carb (µM)

5. Effect of atropine on carbachol log conc response
In the presence of atropine
Curves are shifted to the right - higher concentration of carbachol required
Curves are parallel
Still get the same maximum response
Carbachol is able to overcome the presence of the atropine

6. Antagonist This type is COMPETITIVE antagonism
antagonist competes with agonist for same receptor site
can be surmountable or insurmountable
if surmountable then increasing conc of agonist will overcome the block
sometimes this is known as reversible competitive antagonism
eg ATROPINE competes with CARBACHOL at muscarinic receptors

7. Surmountable antagonism
Agonist and antagonist molecules occupy the same receptor sites
Dynamic process
Drug molecules of both types rapidly associating and disassociating
If agonist conc is increased - more chance of an agonist molecule occupying the receptor
Therefore get a response

8. Insurmountable Antagonism
Again a dynamic situation
BUT rate of dissociation of antagonist may be MUCH SLOWER
Agonist molecule does not get the chance to bind
Unable to overcome the block
This may happen to varying extents
sometimes this is known as irreversible competitive antagonism

9. Insurmountable Antagonism Curve
AGONIST
100 75
AGONIST +
ANTAGONIST
% Maximum response 50 25
0.001
0.01
0.1 1 10
100
log conc (µM)

10. Insurmountable antagonist cont..
if insurmountable, increasing conc of agonist unable to overcome the block
probably because dissociation of the antagonist is very slow
eg -BUNGAROTOXIN on ACh receptors at the neuromuscular junction

11. Competitive Antagonism
Recommended Reading
Competitive Antagonism
Medical Pharmacology at a glance, 5th Ed: Pages 10 & 11
Pharmacology, 5th Ed: Pages and 18 & 19
Basic and Clinical Pharmacology Online Book: Section I, Chapter 2, Relation Between Drug Concentration and Response, Competitive and Irreversible Antagonists