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Transcript
Drugs on the Brain
Emma Robinson
RCUK Academic Fellow
What is Pharmacology?
Pharmacology is the study of the
interaction between chemical substances
(drugs) and living systems
•The word “pharmacology” is derived from
two Greek words:
–pharmakon: a mystical potion or drug
–logos: a rational discussion
What does a Pharmacologist do?
•Study the processes involved in disease
•Identify drug targets – receptors (cells
docking molecules)
•Study how drugs affect the different processes
of the body – effects and side effects
•Study what the body does to the drug
•Study the toxicity of a drug
Aim: The perfect drug!
Reality
All drugs have side effects but new drugs
aim to provide beneficial effects with
minimal side effects
How is this achieved?
1. Identify new molecules
2. Modify structure of know molecules
Test in biological tissue or whole body
Using pharmacological agents
1. Mimic the effects of an endogenous molecule
a) Deficit in the function of the molecule
e.g. Parkinson’s disease
b) Mimicking its action to reduces symptoms of disease
e.g. asthma
2. Blocking the actions of an endogenous molecule
a) Excess of the molecule is causing the disease
e.g. gastric ulcers
b) Blocking its action reduces the symptoms
e.g. hypertension
3. Modulating the amount of the endogenous molecule
e.g. depression
Effects and side effects
•
Drug effects and side effects result from
interaction with individual receptors
•
All drugs interact with more than one receptor
•
Endogenous molecules usually bind to multiple
receptors in the same family
•
Drugs are designed to target specific receptor
subtypes to reduce side effects
• Increasing the concentration of the drug increases
side effects
•
Patients experience different effects and sideeffects
Targeting different systems of
the body
•One endogenous molecule can mediate many
effects by acting at multiple receptors
•Targeting individual receptors can produce
selectivity
•Identify chemical characteristics that make a
drug interact with only one receptor
•Identify the protein target and model drug
binding using computer software
Adrenaline
Prepares the body for fight or flight
•More blood pumps
around the body
•More oxygen gets
into the lungs
Stimulates the heart
Relaxes the airway
Salbutamol – b2-agonist
•Mimics the action of adrenaline in the lungs
•Relaxes the lung tissue
•Used to treat asthma
•Minimal effects on the heart
Propranolol – b-blocker (antagonist)
Stops the effects of adrenaline on the heart
Used to treat:
•Panic attacks
•High blood pressure
Drugs and the brain
Quiz
1. What diseases affect the brain?
2. What drugs affect the function of
the brain?
3. Which brain disorder is the most
common in the UK?
What is neurotransmission?
1. Electrical
2. Chemical
SYNAPSE
Diagram of a synapse demonstrating the release of
a neurotransmitter which binds to receptors on
the adjacent neurone leading to
depolarisation/repolarisation
Neuronal pathways and networks
Image of a neuronal network
Functions associated with specific brain regions
Image of a brain showing the different
regions associated with different functions
How do drugs affect the
brain?
General effects
• Excitation – stimulants
• Inhibition – anaesthetics
Specific effects
• Pathway specific
• System specific
Pictures of the effects of administering these drugs
on the formation of spider’s webs
Normal
Marijuana
Benzedrine
(stimulant)
What drugs
do?
Chloral hydrate
(sedative)
Caffeine
Depression
1. What is depression?
2. Why do people get depressed?
3. How do drugs affect mood?
The limbic system – controller of emotions
Image of a brain showing the limbic system
What makes a good drug for
depression?
1. Improve mood
2. Enhance motivation
3. Rapid effect
4. No side effects
5. Safe
What makes a bad drug for
depression?
1. Lack of effect in all patients
2. Abuse potential
3. Side effects
4. Slow onset of action
5. Low therapeutic index – easy for
patients to overdose
Tricyclic antidepressant
e.g amitryptline
Picture
of the
heart
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Ser
5
NA
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NA
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Mood
Motivation
Drugs which affect mood
1. Stimulants
2. Depressants
3. Mood enhancers
4. Drugs which stimulate reward
Which transmitter is the best
target for an antidepressant?
Serotonin
•
•
Regulates mood and emotion
Evidence that levels are reduced in
depression
 Target the serotonin re-uptake transporters
 Treat symptoms of depression but without
side effects seen with TCA drugs
Improving the drug design
Which property of the TCA
drug increases mood?
TCA Structure interacts with
many different receptors

Multiple effects and side
effects
Serotonin is the major transmitter
Too little
 Depression
 Selective block of serotonin re-uptake
Identify a chemical structure that is
SELECTIVE for serotonin transporters
SSRI = Serotonin specific reuptake inhibitor
Serotonin specific re-uptake
inhibitor e.g Fluoxetine
(Prozac)
Picture
of the
heart
Ser
Ser
5
NA
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Mood
2