Drugs on the Brain Emma Robinson RCUK Academic Fellow
Dec 22, 2015
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?
Diagram of a synapse demonstrating the release of a neurotransmitter which binds to receptors on the adjacent neurone leading to depolarisation/repolarisation
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
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
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