Neuropharmacology

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Neuropharmacology

• Kevin Silber
• University of Derby

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Neuropharmacology
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Drug Classes

• The five groups of psychoactive drug are
• DEPRESSANTS
• STIMULANTS
• OPIATES
• PSYCHEDELICS
• ANTIPSYCHOTICS
• The following two slides show these classes of
  drugs, examples of each class, the
  neurotransmitter affected and the drug action.

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Drug Class and Drug NT Drug Action Depressants Al
cohol GABA Increases binding Barbiturates GABA Inc
reases binding Benzodiazepines GABA Increases
binding Stimulants Amphetamine DA,
NA Increases Cocaine DA, NA Increases Opiates Mor
phine, Heroin Enkephalins Mimic Endorphins Psych
edelics Marijuana Anandemide Mimic LSD 5HT Mimic
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Drug Class and Drug NT Drug Action Antipsychotic
Antischizophrenic Chlorpromazine DA Blocks Antid
epressant MAO Inhibitors 5HT, NA Increase Trycycli
cs 5HT, NA Increase Selective 5HT
ReuptakeInhibitors 5HT Increase
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How drugs work on the nervous system
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What is Cognitive Neuroscience?
Pharmacodynamics
Pharmacodynamics is concerned with a number of
pharmacological issues, including drugreceptor
interactions, doseresponse curves and receptor
activity, therapeutic indices and drug safety and
the competition between antagonists and agonists
for receptor binding.
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What is Cognitive Neuroscience?
Dose Response Curve the EC50
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What is Cognitive Neuroscience?
ADME
Absorption refers to the rate at which a
medication enters the bloodstream. Drug
absorption can be active, facilitated or passive.
Multiple factors modify drug absorption.
Distribution is the rate at which a drug moves to
and from the blood to the tissues of the body and
the relative proportions of drug in the tissues.
influenced by lipid solubility.
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What is Cognitive Neuroscience?
ADME
Metabolism is the removal of a drug from the body
by metabolic transformation of the drug into
other compounds. These processes include phase 1
(oxidative) or phase 2 (conjugative) metabolism.
Elimination is the rate of metabolism for a
medication. Elimination is frequently expressed
as the half-life, which is the length of time
necessary to eliminate 50 of the remaining
amount of drug present.
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What is Cognitive Neuroscience?
Efficacy
Usually demonstrated performing randomised
controlled trials (RCTs) that compare the study
drug with a placebo or a reference drug, in a
group of carefully selected patients. In such
trials, efficacy is assessed by comparing
measures of the effects of the test and reference
drugs using statistical analyses.
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What is Cognitive Neuroscience?
Randomised Controlled Studies
Treatment Group
Follow Up
CompareResults
Random Assignment
Patients
Control Group
Follow Up
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What is Cognitive Neuroscience?
Randomised Controlled Double Blind Method
These are Pill A(placebo)
Please takethese pills
Patient 1
Study Doctor
Please takethese pills
These are Pill B(experimental drug)
Patient 2
Details of which patients received drug and which
received placebo are blind to researchers and
patients
Patient 3
Study Manager
Patient 4
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The Double BlindMethod
A double blind study is the most rigorous
clinical research design. In addition to the
randomisation of subjects which reduces the risk
of bias, it can eliminate the placebo effect
which is a further challenge to the validity of a
study.
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What is Cognitive Neuroscience?
Effectiveness
Effectiveness can only be shown with real world
experimental data. This means that drugs must be
approved and prescribed to individuals in the
general population before data can be generated.
Effectiveness requires the careful use of
epidemiological methods.
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What is Cognitive Neuroscience?
Pharmacokinetics
Pharmacokinetics is concerned with what the body
does to the drug. Pharmacokinetics make a
significant contribution to individual
differences in reactions to a drug.
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Drug Effects on a Receptor
Neurotransmitter binding site
Neurotransmitter
Drug
Drug
Competitive binding
Direct agonist
Direct antagonist
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Drug Effects on a Receptor
Neuro- transmitter
Neuro- transmitter
Drug
Drug
Noncom-petitive binding
Indirect agonist
Indirect antagonist
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EFFECTS ON THE ACETYLCHOLINE SYSTEM

• Drugs which increase ACh activity include
  nicotine (a stimulant) and physostigmine (a
  psychedelic).
• Drugs which decrease ACh activity include
  atropine and scopolamine (psychedelics).
• Hence both ACh excitation and ACh inhibition can
  both lead to psychedelic effects.
• The precise role(s) of ACh in the brain are not
  well known but we can look at the synaptic
  effects of the above-mentione drugs.

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EFFECTS ON THE ACETYLCHOLINE SYSTEM
Ac CoA choline
ACh
atropine and scopolamine
choline acetate
nicotine
AChE
physostigmine
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EFFECTS ON THE CATECHOLAMINE SYSTEMS

• Drugs which increase Dopamine and Noradrenaline
  activity include amphetamine and cocaine
  (stimulants). LSD (psychedilic) mimics serotonin
  (5HT) activity. MAOIs and trycyclics
  (antidepressants) increase noradrenaline and
  serotonin activity. SSRIs (antidepressants)
  increase serotonin activuty.
• Drugs which decrease dopamine activity include
  chlorpromazine (antischizophrenic) and reserpine
  (tranquilizer). Reserpine also affects NA
  activity.
• There are many other drugs which affect the
  catecholamine systems.

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EFFECTS ON THE CATECHOLAMINE SYSTEMS
Tyrosine
DOPA
Dopamine
reserpine
MAOI (e.g. tranylcypromine)
cocaine and trycyclics (e,g, amitrypyline)
amphetamine
apomorphine
chlorpromazine
MAO
COMT
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EFFECTS ON THE CATECHOLAMINE SYSTEMS
Tyrosine
DOPA
Dopamine
reserpine
NA
MAOI (e.g. tranylcypromine)
amphetamine
cocaine and trycyclics (e,g, amitrypyline)
MAOI (e.g. pargyline)
clonidine
MAO
COMT
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EFFECTS ON THE CATECHOLAMINE SYSTEMS

• Drugs which increase the activity of serotonin
  include LSD (psychedelic) and MAOIs (e.g.
  iproniazid), trycyclics (e.g. imipramine and
  amitrypyline) and SSRIs (e.g. fluoxetine), all
  antidepressants.
• Drugs which decrease the activity of serotonin
  include reserpine (tranquilizer).

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EFFECTS ON THE CATECHOLAMINE SYSTEMS
tryptophan
5OHtryptophan
5HT
reserpine
MAOI (e.g. iproniazid)
trycyclics (e.g. imipramine and amitryptyline)
lysergic acid diethylamide
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Serotonin system
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Serotonin Too Much of a Good Thing
Cardiac valve pathology
Too Much Serotonin
Serotonin syndrome fever, tremor, coma,
seizures, death
GI disturbance
Sexual dysfunction
Insomnia
Anxiety
Bulimia
Panic
OCD
Depression
Not Enough Serotonin
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EFFECTS ON THE GABA SYSTEMS

• The major psychoactive drugs which affect the
  GABA system are all compounds which help the
  binding of GABA to its receptor. As GABA is an
  inhibitory neurotransmitter, the action of such
  drugs is to depress the CNS.

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EFFECTS ON THE GABA SYSTEMS
Glutamate
GABA
barbiturates, benzodiazepines