Chapter 4
Psychopharmacology
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Chapter 4 Outline
• Principles of Psychopharmacology
• Sites of Drug Action
• Neurotransmitters and Neuromodulators
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• Principles of Psychopharmacology
• Psychopharmacology
• The study of
_____________________________________________.
• Drug effects
• The changes a drug produces in an animal’s
physiological processes and behavior.
• Sites of _______________
• The locations at which molecules of drugs interact
with molecules located on or in cells of the body,
thus affecting some biochemical processes of
these cells.
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• Drug effects example:
• Effects of opiates (_______________________)
decrease sensitivity to pain, slow down digestion, relax
muscles, constrict pupils, induce euphoria
• Sites of action – specialized receptors in certain neurons
in the CNS.
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• Principles of Psychopharmacology
• Pharm_______________ (movement of drugs)
• The process by which drugs are absorbed,
distributed within the body, metabolized, and
excreted.
Once a drug enters the body it begins to be
______________________________________________
_____________________________________________.
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• Principles of Pharmacology
• Routes of administration
• Intravenous (IV) injection
• Injection of a substance directly into a _____.
• Usually the fastest route
• Intraperitoneal (IP) injection
• The injection of a substance into the
______________________________________________
___________surrounds the stomach,
intestines, liver, and other abdominal organs.
Used with small animals.
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• Principles of Pharmacology
• Routes of administration
• Intramuscular (IM) injection
• Injection of a substance into a muscle. Absorbed by
_________________that supply the muscle.
• ______________________ (SC) injection
• Injection of a substance into the space beneath the skin.
(TB test).
• Oral administration
• Administration of a substance into the mouth, so it is
swallowed. (Some drugs are destroyed by digestive
________________).
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• Principles of Pharmacology
• Routes of administration
• ________________administration
• Administration of a substance by placing it beneath the
tongue. (Nitroglycerine for coronary artery dilation).
• Intrarectal administration
• Administration of a substance into the rectum.
(suppository).
• Inhalation
• Administration of a vaporous substance into the lungs.
(_________________ effects).
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• Principles of Pharmacology
• Routes of administration
• Topical administration
• Administration of a substance absorbed through
the __________. (Nicotine patch).
• Intracerebral administration (Some drugs cannot
cross the _______________________).
• Administration of a substance directly into the brain.
• Intracerebroventricular (ICV) administration
• Administration of a substance into one of the cerebral
ventricles.
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• Principles of Pharmacology
• Drug Effectiveness:
lipid soluble drugs _____ the
blood/brain barrier, water soluble drugs ________.
• Dose-response curve
• Plots the magnitude of the effect of a drug as a
function of the amount of the drug administered.
• Therapeutic index
• The ratio between the dose that produces the
desired effect in 50% of the animals and the dose
that produces ________ effects in 50% of the animals.
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• Most drugs have more than one effect.
• Opiates reduce pain (1), and also depress heart rate
and respiration which can be lethal (2).
• The therapeutic index differs for different classes of
drugs.
• Barbiturates 2-3.
• Tranquilizers (100+).
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• Principles of Pharmacology
• Drug Effectiveness
• ______________:
• The readiness with which two molecules join together.
• High affinity drugs produce effects at low concentrations.
• Low affinity drugs require high concentrations to have an
effect.
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• Principles of Pharmacology
• Effects of repeated administration
• ________________ (most common pattern)
• A decrease in the effectiveness of a drug that is
administered repeatedly.
• __________________ (less common, bee stings)
• An increase in the effectiveness of a drug that is
administered repeatedly.
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• Principles of Pharmacology
• Effects of repeated administration
• ________________ symptom
• The appearance of symptoms opposite to those
produced by a drug when the drug is administered
repeatedly and then suddenly no longer taken.
• ____________
• An inert substance given to an organism in lieu of a
physiologically active drug; used experimentally to
control for the effects of mere administration of a drug.
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• Because drugs may have multiple sites of action, the
drug effect at some sites may show tolerance, but at
other sites tolerance may not be expressed!
• Tolerance is the result of the body’s attempt to
______________ for the effects of the drug.
(Preserve homeostasis).
• Barbituates cause sedation, and depress respiration.
The sedation effect shows tolerance, the depression
of respiration does not!
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• Sites of Drug Action
• ________________
• A drug that opposes or inhibits the effects of
a particular neurotransmitter on the postsynaptic cell.
• _______________
• A drug that facilitates the effects of a particular
neurotransmitter on the postsynaptic cell.
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• Sites of Drug Action
• Effects on receptors
• Direct agonist
• A drug that binds with and activates a receptor. This drug
mimics the effects of a neurotransmitter.
• ________________blocker
• A drug that binds with a receptor but does not
activate it; prevents the natural ligand from binding
with the receptor.
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• Sites of Drug Action
• Effects on receptors
• Direct antagonist
• Synonym for a receptor blocker.
• Noncompetitive binding
• Binding of a drug to a site on a receptor; does not
interfere with the binding site for the principal ligand.
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• Sites of Drug Action
• Effects on receptors
• Indirect antagonist
• A drug that attaches to a binding site on a receptor and
interferes with the action of the receptor; does not
interfere with the binding of the ___________________.
• Indirect agonist
• A drug that attaches to a binding site on a receptor and
facilitates the action of the receptor; does not interfere
with the binding site of the principal ligand.
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• Summary:
• Drugs can
_________________________________________
_________________________________________
_________________________________________
_________________________________________
_________________________________________
_________________________________________
_________________________________________
________________________________________.
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• Overview:
• In the brain most synaptic communication is
accomplished by just two neurotransmitters.
• Glutamate – _______________
• GABA – ___________________
Glycerine – inhibitory in spinal cord & lower brain stem.
• In general the other neurotransmitters serve as
_________________and act to activate or inhibit
entire circuits.
• Ach activates learning circuits, but what is learned is
transmitted by glutamate and GABA neurons.
• Norepinephrine – heightens vigilance.
• Serotonin – suppresses some species-typical behaviors.
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• Neurotransmitters and Neuromodulators
• Acetylcholine
• The primary neurotransmitter secreted by the efferent
axons of the central nervous system.
•
All muscular movement is accomplished by the release of
acetylcholine.
•
Appears to be involved in regulating REM sleep, perceptual
learning, and memory.
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• Neurotransmitters and Neuromodulators
• Acetylcholine
• Acetyl-CoA
• A cofactor that supplies acetate for the synthesis of
acetylecholine.
• Choline acetyltransferase (ChAT)
• The enzyme that transfers the acetate ion from acetyl
coenzyme A to choline, producing the neurotransmitter
acetylcholine.
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• Neurotransmitters and Neuromodulators
• Acetylcholine
• Botulinum toxin
• An acetylcholine antagonist; prevents release
by terminal buttons.
• Black widow spider venom
• A poison produced by the black widow spider
that triggers the release of acetylcholine.
• Neostigmine
• A drug that inhibits the activity of acetylcholinesterase.
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• Neurotransmitters and Neuromodulators
• Acetylcholine
(two receptors)
• _______________receptor
• An ionotropic acetylcholine receptor that is
stimulated by nicotine and blocked by curare. (Rapid
action, used at neuromuscular junction).
• ____________________receptor
• A metabotropic acetylcholine receptor that is
stimulated by muscarine and blocked by atropine.
(Second messenger results in slower and more prolonger
action. This is the main receptor in CNS.)
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• Neurotransmitters and Neuromodulators
• Acetylcholine
• ______________
• A drug that blocks muscarinic acetylcholine receptors. A
belladonna alkaloid extracted from nightshade. This drug
was used to increase _______________.
• Curare
• A drug that blocks nicotinic acetylcholine receptors and
causes paralysis. In surgery a anesthetic must also be
used, because the person is
_________________________________, even though
they are paralyzed.
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• Neurotransmitters and Neuromodulators
• Monoamines
• ______________
• Dopamine (DA)
• Norepinephrine (NE)
• Epinephrine
• Indolamines
• Serotonin (5-HT)
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• Neurotransmitters and Neuromodulators
• _________________
• A class of amines that includes indolamines such
as serotonin and catecholamines such as dopamine,
norepinephrine, and epinephrine.
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• Neurotransmitters and Neuromodulators
• Monoamines
• __________________
• A neurotransmitter; one of the catecholamines.
• Produces both excitatory and inhibitory postsynaptic
potentials.
• Implicated roles in movement, attention, learning,
reinforcing effects of abused drugs.
• Synthesized from tyrosine that we obtain from our diet.
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• Neurotransmitters and Neuromodulators
• Monoamines-dopamine
• L-Dopa
• The biologically active form of DOPA; the precursor
of the catecholamines; often used to treat Parkinson’s
disease because of its role as a dopamine agonist.
Side-effect is heightened_______________.
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• Neurotransmitters and Neuromodulators
• Monoamines-dopamine
• ___________________ system
• A system of neurons originating in the substantia
nigra and terminating in the neostriatum (caudate
nucleus and putamen of the basal ganglia);
appears to play a role in the control of ______________.
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• Neurotransmitters and Neuromodulators
• Monoamines-dopamine
• __________________system
• A system of dopaminergic neurons originating in
the ventral tegmental area and terminating in the
nucleus accumbens, amygdala, and hippocampus;
appears to play a role in the ___________________of
drugs that are commonly abused.
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• Neurotransmitters and Neuromodulators
• Monoamines-dopamine
• _______________ system
• A system of dopaminergic neurons originating in
the ventral tegmental area and terminating in the
prefrontal cortex; appears to influence formation
of short-term memories,
___________________________________________.
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• Neurotransmitters and Neuromodulators
• Monoamines-dopamine
• ________________ disease
• A neurological disease characterized by tremors,
rigidity of the limbs, poor balance, and difficulty
initiating movements; caused by degeneration of
the nigrostriatal system; Parkinson’s disease has
been treated with L-DOPA.
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• Neurotransmitters and Neuromodulators
• Monoamines-dopamine
• AMPT
• A drug that blocks the activity of tyrosine
hydroxylase and thus interferes with the synthesis
of the catecholamines.
• _________________
• A drug that interferes with the storage of
monoamines in synaptic vesicles; serves as a
monoamine antagonist.
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• Neurotransmitters and Neuromodulators
• Monoamines-dopamine
• Methylphenidate
• A drug that inhibits the reuptake of dopamine;
also known as ____________; used to treat children with
attention deficit disorder.
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• Neurotransmitters and Neuromodulators
• Monoamines-dopamine
• _________________________ (MAO)
• A class of enzymes that destroy the monoamines;
dopamine, norepinephrine, and serotonin.
• deprenyl
• A drug that blocks the activity of MAO-B; acts as a
dopamine agonist.
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• Neurotransmitters and Neuromodulators
• Monoamines-dopamine
• _____________________
• A drug that reduces the symptoms of schizophrenia by
blocking dopamine D2 receptors.
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• Neurotransmitters and Neuromodulators
• Monoamines-norepinephrine (NE)
• _________________________
• One of the catecholamines; a neurotransmitter
found in the brain and in the sympathetic division
of the autonomic nervous system.
• Epinephrine
• One of the catecholamines; a hormone secreted
by the adrenal medulla; serves as a neurotransmitter
in the brain. The same molecule can be used as both a
hormone and neurotransmitter.
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• Neurotransmitters and Neuromodulators
• Monoamines-norepinephrine (NE)
•
Norepinephrine is synonymous with nor______________.
•
Found in neurons of the brain and the autonomic nervous
system.
•
Almost every region of the brain receives input from
noradrenergic neurons.
•
Implicated to play central role in
_______________________________________________.
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• Neurotransmitters and Neuromodulators
• Monoamines-norepinephrine (NE)
• Fusaric acid
• A drug that inhibits the activity of the enzyme
dopamine-ß-hydroxylase and thus blocks the
production of norepinephrine. ____________ would be
secreted as a result.
• Locus coeruleus
• A dark-colored group of noradreneric cell bodies located
in the pons near the rostral end of the floor of the fourth
ventricle.
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• Neurotransmitters and Neuromodulators
• Monoamines-norepinephrine (NE)
• Axonal varicosity
• An enlarged region along the length of an axon
that contains synaptic vesicles and releases a
neurotransmitter or neuromodulator.
• Idazoxan
• A drug that blocks presynaptic noradrenergic 2
receptors and hence acts as an agonist, stimulating
the synthesis and release of NE.
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• Neurotransmitters and Neuromodulators
• Monoamines
• _______________
• Serotonin is an indolamine neurotransmitter.
• Also called 5-HT or 5-hydroxytryptamine.
• Thought to play a role in the regulation of _________, the
control of eating, sleep, dreaming, and arousal.
• Also thought to be involved in the regulation of pain.
• The amino acid tryptophan is the precursor of serotonin.
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• Neurotransmitters and Neuromodulators
• Monoamines-serotonin (5-HT)
 PCPA
• A drug that inhibits the activity of tryptophan
hydroxylase and thus interferes with the synthesis
of 5-HT and serves as a serotonergic antagonist.
 Fluoxetine (Prozac)
• A drug that inhibits the reuptake of 5-HT.
• Used to treat depression, obsessive-compulsive
disorder and some anxiety disorders. There are at
least ________________ serotonin receptors.
Different drugs may selectively effect different
receptors.
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• Neurotransmitters and Neuromodulators
• Monoamines-serotonin (5-HT)
 Fenfluramine
• A drug that stimulates the release of 5-HT.
 __________
• A drug that stimulates 5-HT2A receptors.
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• Neurotransmitters and Neuromodulators
• Monoamines MDMA
• A drug that serves as a noradrenergic and
serotonergic agonist, also known as _____________
has excitatory and hallucinogenic effects. MDMA
damages serotonin pathways.
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• Neurotransmitters and Neuromodulators
• Amino acids
• The most common amino acid transmitters are:
• Glutamate
• Gamma-aminobutyric acid (GABA)
• Glycine
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• Neurotransmitters and Neuromodulators
• Monoamines-glutamate
 _______________
• An amino acid; the most important excitatory
neurotransmitter in the brain.
 NMDA receptor
• A specialized ionotropic glutamate receptor that
controls a calcium channel that is normally blocked by
Mg2+ ions; has several other binding sites.
 AMPA receptor
• An ionotrpoic glutame receptor that controls a sodium
channel; stimulated by AMPA.
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• Glutamate receptors:
• Three types of iontropic glutamate receptors.
• Seven subtypes of metabotropic glutamate
receptors.
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• Neurotransmitters and Neuromodulators
• Amino acids—glutamate
• Kainate receptor
• An ionotropic glutamate receptor that controls
a sodium channel; stimulated by kainic acid.
• Metabotropic glutamate receptor
• A category of metabotropic receptors sensitive to
glutamate.
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• Neurotransmitters and Neuromodulators
• Amino acids—glutamate
• AP5
• A drug that blocks the glutamate binding site
on NMDA receptors and impairs certain forms
of learning.
• PCP (Phencyclidine)
• A drug that binds with the PCP binding site of the
NMDA receptor and serves as an indirect antagonist
of glutamate.
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• Neurotransmitters and Neuromodulators
• Amino acids
• GABA
• Gamma-aminobutyric acid is an amino acid.
• GABA is the most important ______________
neurotransmitter in the brain and spinal cord.
• Allyglycine
• A drug that inhibits the activity of GAD and thus blocks
the synthesis of GABA.
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• Neurotransmitters and Neuromodulators
• Amino acids—GABA
• ______________
• A direct agonist for the GABA binding site on
the GABAA receptor.
• Bicuculline
• A direct antagonist for the GABA binding site on
the GABAA receptor.
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• Neurotransmitters and Neuromodulators
• Amino acids—GABA
• ___________________
• A category of anxiolytic drugs; an indirect agonist
for the GABAA receptor; these drugs are used for
their tranquilizing effects.
• Examples of these drugs include Valium (diazepam)
and Librium (chlordiazepoxide).
• ___________________
• An anxiety-reducing effect.
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• The brain does not produce valium, barbituates, or
picrotoxin. What are the natural ligands for these
binding sites?
• Research has not answered this question.
It is
assumed that these binding sites are not an accident,
and that brain chemicals use them, but they have not
yet been identified.
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• Neurotransmitters and Neuromodulators
• Amino acids
• ______________
• It appears to be the most important inhibitory
neurotransmitter in the lower brain stem and spinal cord.
• Strychnine
• A direct antagonist for the glycine receptor.
• Causes convulsions and death even in small doses.
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• Neurotransmitters and Neuromodulators
• Peptides (Two or more amino acids linked
together by peptide bonds)
• Neurons of the central nervous system release a large
variety of peptides.
• A neuron manufactures both the polypeptides and the
enzymes that it needs to break them apart.
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• Neurotransmitters and Neuromodulators
• Peptides
• Synthesis takes place in the soma. They are delivered to
the terminal buttons by axoplasmic transport.
• Most peptides appear to serve as ______________,
while some act as neurotransmitters.
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• Neurotransmitters and Neuromodulators
• Peptides
• __________________opioid
• A class of peptides secreted by the brain that act as
opiates; drugs that effect opioid receptors reduce ______.
• Enkephalin
• One of the endogenous opioids.
• At least three different opioid receptors.
• Naloxone
• A drug that blocks opioid receptors; often used to treat
heroin overdose.
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• Neurotransmitters and Neuromodulators
• Lipids
• Endocannabinoid
• A lipid; an endogenous ligand for receptors that bind with
______, the active ingredient of marijuana.
• Anandamide
• The first cannabinoid to be discovered and probably the
most important one.
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• Neurotransmitters and Neuromodulators
• Lipids
• Rimonabant
• A drug that blocks cannabinoid CB1 receptors.
• THC produces analgesia, sedation, reduces nausea,
stimulates appetite, but impairs concentration and
memory. May distort time perception and change
sensory perception. THC can be
______________________________________________
______________, the THC is _________________into
the CNS.
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• Neurotransmitters and Neuromodulators
• Nucleosides
• Adenosine
• A combination of ribose and adenine.
• Released by glial cells and neurons.
• Dilates blood vessels and increases supply of cellular
nutrients.
• ________________
• A bitter-tasting alkaloid drug that blocks adenosine
receptors. Adenosine tends to suppress neural activity,
and caffeine counters this suppression.
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• Neurotransmitters and Neuromodulators
• Soluble gases
• _________________ (NO)
• A gas produced by cells in the nervous system;
used as a means of communication between cells.
Influences blood vessel dilation, and may play a role in
sexual arousal.
• Nitric oxide synthase
• The enzyme responsible for production of nitric
oxide.
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