Drugs on the Brain Emma Robinson RCUK Academic Fellow.

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Presentation 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? 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 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 More blood pumps around the body More oxygen gets into the lungs Relaxes the airway Stimulates the heart

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 What diseases affect the brain? What drugs affect the function of the brain? Which brain disorder is the most common in the UK?

What is neurotransmission? 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 What is depression? Why do people get depressed? 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? Improve mood Enhance motivation Rapid effect No side effects Safe

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

Tricyclic antidepressant e.g amitryptline 5 Picture of the heart Ser NA 1 2 Ser NA 3 4 Mood Motivation

Drugs which affect mood Stimulants Depressants Mood enhancers 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 re-uptake inhibitor

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