General Prinicples of

Pyschopharmacology

Pharmacology

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Neuropharmacology

• Definition
• – “the study of the effects of drugs on the
nervous system and … on behavior”

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General consideration
• composition of nervous system:
• central and peripheral nervous systems.
• neuron and synapse.
• function of CNS:
• regulation of body function
• activity of neuron
• conduction of impulse
• AP - sodium, calcium, potassium, chloride
• Ione channel, voltage-gated, ligand-gated
• neurotransmitter:
• NA,Ach,DA,GABA,glutamate,glycine,5HT, histamine,
opioid peptides and tachykinins.
• Flashback:
− biosynthesis, storage, release, degradation, re-uptake.

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General consideration …..
• Receptors
• Give a classification of synaptic
receptors ????
• Conduction of impulse across synapse
• presynaptic neuron release
neurotransmitter  synaptic cleft 
neurotransmitter interacts with receptor 
neurotransmitter-receptor complex initiates a
sequence of events (open ion channel)
modulate the electrical activity of the
postsynaptic neuron (depolarization/
hyperpolarization)
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mechanism of drug on CNS

• axon:
• slow or block the axonal electrical
conduction. , e.g. local anaesthetics
• synapse:- most drugs will
• affect transmitter.
• affect receptor.
• directly act on ion channel.

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Brain Neurotransmitters

• Amines • Neuropeptides
• Serotonin • CRH, CRF
• Dopamine • TRH, LHRH
• Norepinephrine • GH, somatostatin
• Epinephrine • Opioid Peptides
• Acetylcholine • Dynorphin
• Amino Acids • ß-endorphin
• GABA • Gut hormones
• Glycine • CCK, secretin
• Glutamic Acid • Substance P

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Review of Neurotransmitters
• Acetylcholine
• Release accomplishes muscular movement
• Easy to study because is found outside the CNS
• First neurotransmitter to be discovered
• Generally a facilitator
• Two types of receptors
• Ionotropic (nicotinic) – opening of ion channels; direct
effect
• Metabotropic (muscarinic) – longer lasting, change
metabolic character of postsynaptic neuron

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Review of Neurotransmitters:
The Monoamines
• Dopamine
• Both excitatory and inhibitory postsynaptic
potentials
• Functions: movement, attention, learning,
reinforcing effects of abused drugs
• Synthesis:
• Tyrosine + enzyme = L-DOPA + enzyme = Dopamine
• Parkinson’s disease (movement disorder) caused
by degeneration of dopaminergic neurons
• L-DOPA is the treatment  converted to Dopamine by
surviving dopaminergic neurons

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Review of Neurotransmitters:
The Monoamines
• Noradrenaline
• Found in the autonomic nervous system
• Gives input to almost every region of the
brain
• Activation causes and increase in
attentiveness to events in the environment
• Synthesis:
• Tyrosine + enzyme = L-DOPA + enzyme =
Dopamine + enzyme = Norepinephrine
• Adrenaline is also a neurotransmitter
• less important than noradrenaline

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Review of Neurotransmitters:
The Monoamines
• Serotonin
• Deals with regulation of mood; control of
eating, sleep, and arousal; regulation of pain
• Somehow involved in dreaming
• Bodies of serotonergic neurons found in the
raphe nuclei or midbrain, pons, and medulla
• “Drugs that inhibit the reuptake of serotonin
have found a very important place in the
treatment of mental disorders.”

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Neurotransmitters:
Amino Acids
• Glutamate
• Principle excitatory neurotransmitter in
brain and spinal cord
• 4 major types of receptors:
• NMDA receptor – glutamate binds here (along
with glycine) and opens a calcium channel
• AMPA receptor
− (α-amino-3-hydroxy-5-methyl-isoxazole)
• Kainate receptor
• Metabotropic Glutamate receptor

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Neurotransmitters:
Amino Acids…..
• GABA
• Glutamic acid + enzyme = GABA
• Most important inhibitory
neurotransmitter
• Epilepsy is thought to be caused by a
problem with GABA-secreting neurons or
GABA receptors
• Glycine
• Inhibitory neurotransmitter in spinal cord
and lower brain
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Drug Effects on
Neurotransmitters
• Most drugs affect synaptic transmission
• Agonist – a drug that facilitates the action
of a neurotransmitter
• Direct agonist – fits into receptor sites on
postsynaptic cell and mimics action of
neurotransmitter
• Antagonist – a drug that reduces the
action of a neurotransmitter
• Direct antagonist – fits into receptor sites of
postsynaptic cell and blocks effects of
neurotransmitter
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Agonists
• Various mechanisms of action of agonists:
• Drug serves as a precursor
• Drug stimulates release of neurotransmitter
• Drug stimulates postsynaptic receptors
(direct agonist)
• Drug blocks autoreceptors; increases
neurotransmitter synthesis/release
• Drug blocks reuptake
• Drug inactivates acetylcholinesterase
• Leaves acetylcholine in the synapse so that the effect
lasts longer

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Antagonists
• Various mechanisms of action of
antagonists:
• Drug inactivates synthetic enzyme;
inhibits synthesis of neurotransmitter
• Drug prevents storage of neurotransmitter
in vesicles
• Drug inhibits release of neurotransmitters
• Drug blocks postsynaptic receptors (direct
antagonist)
• Drug stimulates autoreceptors; inhibits
synthesis/release of neurotransmitters
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Drug Classifications and Their
Relation to Neurotransmitters

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Tranquilizers/Sedative-
Hypnotics
• “Downers”
• Barbiturates and Benzodiazepines
• They act on GABA – inhibitory
neurotransmitter
• Facilitate GABA receptors
• Increase the change of opening GABA
receptor
• Increase the frequency and the time open
• Directly inhibit the Nucleus Accumbens
through GABA receptors
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Antipsychotics
• Schizophrenia
• Dopamine Hypothesis: Schizophrenia
results from excess dopamine in the
mesolimbic pathways in the brain
• Antipsychotics block dopamine receptors
• Used for the treatment of Schizophrenia
• reduces positive symptoms
• Antipsychotics are also weak serotonin
inhibitors
• Not sure what this does for Schizophrenia

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Antidepressants
• Depression
• Serotonin Hypothesis: Depression results
from low serotonin levels
• Antidepressants increase serotonin
• MAOIs (Monoamine oxidase inhibitors)
prevent the breakdown of serotonin in the
synaptic cleft
• SSRIs (Selective Serotonin Reuptake
inhibitors) prevent the reuptake of
serotonin into the presynaptic neuron

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Psychomotor Stimulants
• “Uppers”
• Cocaine, Methamphetamine, Amphetamines
• Stimulate monoamine transmission
• Dopamine, epinephrine, norepinephrine
• Dopamine
• Increase levels by blocking reuptake
• Activates dopaminergic reward and motor
pathways
• Adrenaline
• Activates sympathetic nervous system through
adrenaline

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Opiates

• Opiates are generally inhibitory

neurotransmitters
• Opiates activate opiate receptors
• Leads to inhibition of the Nucleus
Accumbens which causes activation of the
Ventral Tegmental Area and the
Mesolimbic Dopamine system

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Hallucinogens
• Neurophysiology is not well understood
• Serotonin-like
• Block serotonergic transmission
• Noradrenaline-like
• Acetylcholine-like
• Block cholinergic synapses

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Classification of Psychotropics
parameter effect group
watchfulnes positive psychostimulant drugs
(vigility)
negative hypnotic drugs

affectivity positive antidepressants

anxiolytics
negative dysphoric drugs
psychic positive neuroleptics, atypical
integrations antipsychotics
negative hallucinogenic agents
memory positive nootropics
negative amnestic drugs
 Main Psychotropic Drugs

 Antipsychotics
 Antidepressants
 Anxiolytics
 Hypnotics
 Cognitives
 Psychostimulants
 Hallucinogens
 Potential Action of Psychotropics
1. Synthesis and storage of
neurotransmitters
2. Releasing of neurotransmitters
3. Receptor-neurotransmitter
interactions (agonists, antagonists)
4. Catabolism of neurotransmitters
5. Reuptake of neurotransmitters
6. Transduction element (G protein)
7. Effector's system
8. Transcription factor activity and gene
expression
SUMMARY Antidepressant
Antidepressant //
Tri-Cyclic
Tri-Cyclic
Antidepressa
Antidepressa
nt
escitalopram (Lexapro)
Anxiolytic
Anxiolytic nt
MAOIs
MAOIs

Benzodiazepines
Benzodiazepines lorazepam (Ativan)
diazepam (Valium)

GABA
GABA zolpidem (Ambien)
Antagonist
A
Antagonist

Phenytoin-Like
phenytoin (Dilantin)
Phenytoin-Like
Drugs
Drugs valproic acid (Depakote)

Succinimides
Succinimides ethosuximide (Zarontin)

Barbiturates
Barbiturates phenobarbital (Luminal)

Phenothiazines
Phenothiazines chlorpromazine (Thorazine)

Non-
Non- halperidol (Haldol)
Phenothiazines
Phenothiazines
Opioids
Opioids
morphine (Infumorph) Atypical
Atypical
Antipsychotics risperidone (Risperdal)
Salicylates
Salicylates aspirin (ASA) Antipsychotics

NSAIDs
NSAIDs ibuprofen (Motrin)
Non-Opioid
Non-Opioid acetaminophen (Tylenol)
Central
Central Acting
Acting tramadol (Ultram)

Anti-Migraine ergotamine (Cafergot)

Anti-Migraine
Sumatriptan (Imitrex)
Opioid
Opioid naloxone (Narcan)
Antagonists
Antagonists
OTHERS
Methylxanthines (Caffeine)
• Adenosine – neuromodulator that inhibits
release of many neurotransmitters
• Methylxanthines blocks adenosine receptors
• Long-term use leads to increased number of
adenosine receptors
• Adenosine is important for sleep  blockage of
adenosine receptors keeps a person awake
• adrenaline
• Caffeine increases the release of adrenaline
• Possible cause of caffeine’s stimulating effects

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Alcohol
• Alcohol affects more neurotransmitter systems than
any other drug
• Glutamate – excitatory neurotransmitter
• Alcohol blocks NMDA receptors
• Blocks the excitatory receptors  slows the brain
• NMDA receptors let Na+ and Ca2+ into the cell  alcohol blocks
these from getting into the cell
• Long-term use leads to more NMDA receptors (brain
compensates and makes more)
• GABA – inhibitory neurotransmitter
• Alcohol enhances function of GABA receptors, leading to
greater levels of inhibition
• Body compensates by decreasing function of GABA related
ion channels
• Responsible for withdrawal symptoms
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Tobacco

• Acetylcholine
• Nicotine acts on nicotinic Ach receptors
• At low doses, stimulates nicotinic
receptors
• Opens ion channels
• At high does, blocks nicotinic receptors
• Prevents opening of ion channels

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