Pharmacodynamics: Drug-Receptor

Interactions

Drug Receptors
Receptor:

Synonym: Target molecule

Macromolecule (or macromolecular complex)

which binds agonists with high structural selectivity

with the consequence that a characteristic effect occurs

Or site of drug action responsible for the pharmacological

effect

The component of the organism with which the chemical

agent was presumed to interact.

Receptors can be any functional macromelecular

component of the organism

Drug Binding Sites

(Receptors and Acceptors)

Binding Site

Specific and Saturable

Receptor

Binding Site + Effect

Acceptor

Binding Site + no Effect

Types of Binding
Reversible

ionic attraction, hydrogen bonds, Van der

Waals interactions
Slowly reversible/irreversible
high affinity non-covalent binding,
covalent binding

Specific receptors and Non-specific drug

targets
Non-specific drug targets

- Water
- H+ ion, HO- ion
- Metal ions as relatively specific
receptors

Specific Receptors (drug receptors)

- Enzymes
- Membrane sterols / proteins
- DNA

Differences between

Specific Receptors and Non-specific Drug

Targets
Specific receptors
are stereoselective
can be selectively

blocked by antagonist
drugs
are occupied at
nanomolar or
micromolar
concentrations

Ligands (Receptor binding molecules)

Drugs or endogenous compounds binding to

receptors are described as Ligands.

Ligands are classified into 2 groups

Agonist:
Agonist molecule that binds to receptor and produces

similar response to that of the endogenous ligand.

Partial agonist: agonist that produce partial effect.

Antagonist:
Antagonist molecule that binds to a receptor, but

does not cause a response.

Competitive: reversible or weak binding

Non-competitive: non-reversible or strong binding

Ligands (Agonist and

Antagonist)

Affinity and Efficacy

Affinity: the attraction of the drug for

the receptor.

high affinity: low concentrations bind

low affinity: high concentrations bind
no affinity: does not bind

Efficacy: the intrinsic activity

Max. effect
efficacy = 1
Min. effect
efficacy = 0

Agonist and Antagonist

Agonist

Partial agonist
Antagonist
Competitive

Non-competitive

Affinity
yes
yes

Efficacy
high
low

low-medium
high

no
no

Classifications of Drug Receptors

Drug classification can be based on several
things
Classified by
General characteristics
Location

Consequence of interaction
Secondary chemical messenger involved in the

transduction pathway

Classifications of Drug Receptors

Based on General characteristics

Based on general characteristics, drug receptors
can be classified into 4 groups
Classical Receptors
Or Physiological receptors

Uptake carriers or Transport proteins

Ion channels
Enzymes

Classifications of Drug Receptors

Based on Location

Example 1 Receptors of the nervous system

Post-synaptic receptor: In postsynaptic cells, neurotransmitter receptors
receive signals that trigger an electrical signal, by regulating the activity of
ion channels.
Pre-synaptic receptor: On presynaptic cells the binding of a neurotransmitter
to a specific receptor provides feedback and mediates excessive
neurotransmitter release.
Example 2 Receptors that are on the surface and inside the cells
Cell-surface receptor

Ion-channel-linked receptors
G-protein-linked receptors
Enzyme-linked receptors

Intracellular receptor

Classifications of Drug Receptors

Based on Consequence of
Interaction
Stimulation or Inhibition
Of an enzyme
Of an organ activity

Stimulate or Inhibit heart contractility

Contraction or Relaxation of muscle

Classifications of Drug Receptors

Based on Secondary Messengers

Secondary messengers of the signal transduction

processes are in different kinds and can be used

to classify the receptors connected to them.
Drug

Receptors

Cyclic AMP
Cyclic GMP
Phosphoinositol
Arachidonic acid
Calcium ion

Effector or Target

Drug-Receptor Interaction
Structure specific

Drug + Receptor

Stereo-selective
Lock and key mechanism

Affinity

Drug-receptor complex
Transduction
pathways

Response
Efficacy
Potency

Receptor-mediated Mechanism of Action

drugs

beneficial effect
caused by the drugs ability to interact
with the receptor and change in
physiological

or biochemical
or pathological processes

Then termed mechanism of drug action

Intermediate Messengers or Second

Messengers

Activation of a receptor may initiate a series of

events mediated by intermediate messengers.
Drug

Binding Site

Signal transduction

intermediate
messengers
e.g. cyclic AMP

Effect

Mechanism of action

Classical Receptors

Drug actions on Classical receptors are based on

types of Ligands
Agonist

Antagonist

->

Stimulation
->
Inhibition

Neurotransmitter

norepinephrine (NE)

Hormones

angiotensin

Local hormones
histamine

receptor

receptor
receptor

action

action
action

Mechanism of action

Uptake Carriers

Uptake carriers or Transport

proteins can have a role in

regulation of drug action
Example: Norepinephrine (NE)
action

Drug
Uptake inactivation

Nerve Cell
NE

X
NE release from nerve

More NE
Receptors
Increase NE action

Neurotransmission

Uptake carrier
Reuptake
Rapid inactivation
Decrease NE action

Mechanism of action
Ion Channels
drug - ion channel
enhances /inhibits action
e.g.

Ca++ channel blocker (verapamil)

Mechanism of action

Enzymes

drug-enzyme interaction

inhibition of enzyme activity

Neostigmine inhibits acetyl cholinesterase

increased acetyl choline
Aspirin inhibits cyclooxygenase
decreased prostaglandins

Inhibition of Enzyme Activity Neostigmine

Mechanism of of action:
anti-cholinesterase
Inhibits activity of acetylcholinesterase
Effects: increase
Acetylcholine (ACh) levels
in the synapse.
Clinical use: treatment of
myasthenia gravis

Action of Neostigmine
Somatic Nervous
System (voluntary)

ACh

N
N

AChE

Skeletal
Muscle
N

Neostigmine
acetate

Nicotinic ACh
receptor

choline

Inhibition of Enzyme Activity

Aspirin
Mechanism of action: cyclo-oxygenase inhibitor
Pharmacological effects: prostaglandin release
pain and fever
Clinical use: treatment of pain and fever

Inflammation
and COX
Infection
Arachidonic Acid
(released from cell membrane)
Cyclooxygenase (COX)

Prostaglandins
Pain

Fever

Action of Aspirin
Infection

Arachidonic Acid (released from cell membrane)

Cyclooxygenase
Prostaglandins
Pain

Fever

Aspirin