Drugs on the Brain

Emma RobinsonRCUK 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 molecules2. Modify structure of know molecules

Test in biological tissue or whole body

Using pharmacological agents

1. Mimic the effects of an endogenous moleculea) Deficit in the function of the moleculee.g. Parkinson’s diseaseb) Mimicking its action to reduces symptoms of disease e.g. asthma

2. Blocking the actions of an endogenous moleculea) Excess of the molecule is causing the disease e.g. gastric ulcersb) 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 side-effects

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

Stimulates the heart Relaxes the airway

•More blood pumps around the body

•More oxygen gets into the lungs

Salbutamol – 2-agonist

•Mimics the action of adrenaline in the lungs•Relaxes the lung tissue •Used to treat asthma•Minimal effects on the heart

Propranolol – -blocker (antagonist)

Used to treat:•Panic attacks•High blood pressure

Stops the effects of adrenaline on the heart

Drugs and the brainQuiz

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

What drugs do?

Normal Marijuana Benzedrine(stimulant)

Chloral hydrate(sedative)

Caffeine

Pictures of the effects of administering these drugs on the formation of spider’s webs

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 antidepressante.g amitryptline

NA

NA

Ser

Ser21

3 4

5

Mood

Motivation

Picture of the heart

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

TCA Structure interacts with many different receptors

Multiple effects and side effects

Improving the drug design

Which property of the TCA drug increases mood?

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

Serotonin specific re-uptake inhibitor e.g Fluoxetine

(Prozac)

NA

NA

Ser

Ser21

3 4

5

Mood

Picture of the heart