1. Drugs on the Brain
Emma Robinson
RCUK Academic Fellow

2. 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

3. 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

4. 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?
Identify new molecules
2. Modify structure of know molecules
Test in biological tissue or whole body

5. 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

6. 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 side-effects

7. 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

8. Adrenaline Prepares the body for fight or flight
More blood pumps around the body
More oxygen gets into the lungs
Relaxes the airway
Stimulates the heart

9. Salbutamol – b2-agonist
Mimics the action of adrenaline in the lungs
Relaxes the lung tissue
Used to treat asthma
Minimal effects on the heart

10. Propranolol – b-blocker (antagonist)
Stops the effects of adrenaline on the heart
Used to treat:
Panic attacks
High blood pressure

11. Drugs and the brain Quiz
What diseases affect the brain?
What drugs affect the function of the brain?
Which brain disorder is the most common in the UK?

12. What is neurotransmission?
Electrical
2. Chemical
SYNAPSE

13. Diagram of a synapse demonstrating the release of a neurotransmitter which binds to receptors on the adjacent neurone leading to depolarisation/repolarisation

14. Neuronal pathways and networks
Image of a neuronal network

15. Functions associated with specific brain regions
Image of a brain showing the different regions associated with different functions

16. How do drugs affect the brain?
General effects
Excitation – stimulants
Inhibition – anaesthetics
Specific effects
Pathway specific
System specific

17. 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

18. Depression What is depression? Why do people get depressed?
How do drugs affect mood?

19. The limbic system – controller of emotions
Image of a brain showing the limbic system

20. What makes a good drug for depression?
Improve mood
Enhance motivation
Rapid effect
No side effects
Safe

21. What makes a bad drug for depression?
Lack of effect in all patients
Abuse potential
Side effects
Slow onset of action
Low therapeutic index – easy for patients to overdose

22. Tricyclic antidepressant e.g amitryptline5
Picture of the heart
Ser NA 1 2
Ser NA 3 4
Mood
Motivation

23. Drugs which affect mood
Stimulants
Depressants
Mood enhancers
Drugs which stimulate reward

24. 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

25. 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 re-uptake inhibitor

26. Serotonin specific re-uptake inhibitor e.g Fluoxetine (Prozac)5
Picture of the heart
Ser NA 1 2
Ser NA 3 4
Mood