This document provides an overview of receptor pharmacology and key concepts. It defines drugs and how they act through receptors and other targets. It explains the terms agonist, antagonist, affinity, efficacy and potency. It describes competitive and non-competitive antagonism and their effects on concentration-response curves. The learning objectives are to understand these pharmacological concepts and be able to interpret graphs of drug-receptor interactions.

1. Introductory Pharmacology
General Principles of Drug Action
and Receptor Pharmacology
Professor John Peters
(e-mail: j.a.peters@dundee.ac.uk)

2. Recommended Texts
Medical
Pharmacology at a
Glance (2012, 7th.
ed.) Neal, M.J. Wiley-
Blackwell. ISBN 780-
0-470-65789-8
Pharmacology (2015, 8th.
ed.) Rang, H.P., Ritter,
J.M., Flower, R.J and
Henderson, G. Churchill
Livingstone (Elsevier).
ISBN 978-0-7020-5362-7
Medical Sciences (2014,
2nd. ed.) Naish, J. and
Syndercombe Court, D.
(eds.) Saunders
(Elsevier). ISBN 978-0-
7020-5138-8
Succinct coverage –
ideal for revision of
the basics throughout
years 1-3
Detailed text – an
excellent coverage of all
aspects of Pharmacology
in years 1-3
Multidisciplinary text –
covers basic concepts and
some clinical aspects in
years 1-3

3. Learning Objectives- receptor pharmacology
Following this PowerPoint, students should be able to:
 Provide a definition of a drug
 Understand the terms ‘agonist’, ‘antagonist’ and ‘ligand’
 Understand what is meant by the terms ‘affinity’, ‘efficacy’ and ‘potency’
 Interpret agonist concentration (or dose) responses curves drawn on linear,
or semi-logarithmic, axes and be able to locate the EC50 of an agonist
 Explain what is meant by competitive and non-competitive antagonism
 Provide a description of the effect of a competitive, or non-competitive,
antagonist upon the concentration response curve for an agonist acting
at the same population of receptors

4. Pharmacology
 The study of the manner in which the
function of living tissues and organs
is modified by chemical substances
 The study of drugs – what they are,
how they work, what they do
Pharmacology comprises:
Pharmacodynamics – what a drug
does to the body (biological effects
and mechanism of action)
Pharmacokinetics – what the body
does to a drug (absorption,
distribution, metabolism and excretion
of drugs and their metabolites)

5. Narrowly:
 Any synthetic or natural substance used in the
treatment, prevention, or diagnosis of disease
What is a drug?
More broadly:
 Everyday substances (caffeine, nicotine, ethyl
alcohol)
For a drug to be useful as a therapeutic agent, it must
usually act with a degree of selectivity
 Food additives
 Illicit substances (cannabis, heroin, cocaine)

6. How do drugs act? (1)
Drugs act by binding to target molecules
Selectivity results from:
The chemical structure of the
drug
The target recognising only
ligands of a precise type

7.  Enzymes
Important additional targets are:
 Receptors
 Ion channels
 Carrier molecules (transporters and pumps)
How do drugs act? (2)
Most drugs act by binding to regulatory
proteins, namely:
 DNA
 RNA

8. Receptors and Drugs
Drugs acting on receptors may be either agonists or
antagonists
 Receptors are macromolecules that mediate the
biological actions of hormones and
neurotransmitters
 An antagonist is drug that blocks the actions of
an agonist
 An agonist is a drug that binds to a receptor to
produce a cellular response

9. Agonists
 Agonists bind to receptors to activate them
 Agonists possess affinity and efficacy
Activation step
(efficacy)
Binding step
(affinity)
Receptor (R)
Agonist (A)
A + R AR AR*
Response

10. A + R AR
Low affinity
A + R AR
Medium affinity
A + R AR
High affinity
Affinity is ‘strength of association’ between ligand and
receptor
Fast dissociation rate
Moderate dissociation rate
Slow dissociation rate

11. AR AR*
Response
Efficacy is the ability of an agonist to evoke a cellular
response
Low efficacy
AR AR*
Response
High efficacy

12. Antagonists
Binding step
(affinity)
Receptor (R)
Antagonist (B)
B + R BR
Antagonists block receptor activation by agonists
Antagonists bind to receptors but do not activate them
Antagonists possess affinity but lack efficacy

13. Agonist at low
concentration
Agonist at moderate
concentration
Agonist at high
concentration
Agonist concentration
Receptoroccupancy(%)
0
50
100
The Relationship Between Agonist
Concentration and Receptor Occupancy

14. Concentration (or dose) response relationship
- linear plot
0 50 100 150 200 250 300
Agonist concentration (or dose) (arb. units)
0
20
40
60
80
100
Response(%maximum)
EC50 (or ED50)
The relationship between concentration (or dose) and response is hyperbolic
EC50 is the concentration of agonist that elicits a half maximal response

15. The relationship between concentration (or dose) and response is sigmoidal
Concentration (or dose) response relationship
- semi-logarithmic plot
Agonist concentration (or dose) (arb. units)
Response(%maximum)
0.1 1 10 100 1000
0
20
40
60
80
100
EC50 (or ED50)
EC50 is the concentration of agonist that elicits a half maximal response

16. The meaning of potency and efficacy
B
C
A
10000.01 0.1 1 10 100
Agonist concentration (or dose) (arb. units)
0
20
40
60
80
100
Response(%maximum)
decreasingincreasing
Efficacy
increasing decreasing
Potency
A & B are full agonists
A is a more potent agonist than B but has equal efficacy
C is a partial agonist with a lower efficacy than either A or B
A & C are equipotent

17. Competitive antagonism
Antagonist (B) Agonist (A)
Receptor activeReceptor inactive
 Binding of agonist and antagonist occur at the same (orthosteric)
site and is thus competitive and mutually exclusive

18. Antagonist (B) Agonist (A)
Receptor inactive
 Agonist binds to orthosteric site and antagonist binds to separate
allosteric site and thus is not competitive. Both may occupy the
receptor simultaneously, but activation cannot occur when
antagonist is bound
Non-competitive antagonism

19. Competitive and non-competitive
antagonism
0.01 0.1 1 10 100 1000
Agonist concentration (or dose) (arb. units)
0
20
40
60
80
100
Response(%maximum)
Agonist
+
Competitive
antagonist
Agonist alone
Agonist
+
Non-Competitive
antagonist

20. Summary
Receptors are mostly protein macromolecules
Agonists activate receptors to initiate cellular responses.
They possess affinity and efficacy. Partial agonists have
a lower efficacy than full agonists
Antagonists bind to receptors and block the effect of
agonists. They possess affinity, but not efficacy
Antagonists may act either competitively, or non-
competitively
Competitive antagonists cause a parallel rightward shift of
the agonist concentration response curve with no
depression of the maximal response. Non-competitive
antagonists depress the slope and maximum of the
concentration response curve, but do not cause a rightward
shift