Transcript Document
Chapter 4
Psychopharmacology
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Psychopharmacology
Psychopharmacology:
• The study of the effects of drugs on the nervous
system and on behavior.
Drug effects:
• The changes a drug produces in an animal’s
physiological processes and behavior.
Sites of Action:
• 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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Principles of Psychopharmacology
Pharmacokinetics
Pharmacokinetics:
• The process by which drugs are absorbed,
distributed within the body, metabolized, and
excreted.
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Principles of Pharmacology
Routes of Administration
Intravenous (IV) injection:
• Injection of a substance directly into a vein.
Intraperitoneal (IP) injection:
• The Injection of a substance into the peritoneal
cavity-the space that surrounds the stomach,
intestines, liver, and other abdominal organs.
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Principles of Pharmacology
Routes of Administration
Intramuscular (IM) injection:
• Injection of a substance into a muscle.
Subcutaneous (SC) injection:
• Injection of a substance into the space beneath
the skin.
Oral administration:
• Administration of a substance into the mouth, so
it is swallowed.
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Principles of Pharmacology
Routes of Administration
Sublingual administration:
• Administration of a substance by placing it
beneath the tongue.
Intrarectal administration:
• Administration of a substance into the rectum.
Inhalation:
• Administration of a vaporous substance into the
lungs.
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Principles of Pharmacology
Routes of Administration
Topical administration:
• Administration of a substance by placing it
beneath the tongue.
Intracerebral administration:
• 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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Distribution of Drugs Within the Body
Depot Binding:
• Binding of a drug with various tissues of the body
or with proteins in the blood.
Albumin:
• A protein found in the blood, serves to transport
free fatty acids and can bind with some lipid
soluble drugs.
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Principles of Pharmacology
Drug Effectiveness
Dose-response curve:
• A graph of the magnitude of an 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 toxic effects in 50% of the animals.
Affinity:
• The readiness with which two molecules join
together.
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Principles of Pharmacology
Effects of Repeated Administration
Tolerance:
• A “decrease” in the effectiveness of a drug that is
administered repeatedly.
Sensitization:
• An “increase” in the effectiveness of a drug that is
administered repeatedly.
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Effects of Repeated Administration
Withdrawal symptom:
• The appearance of symptoms opposite to those
produced by a drug when the drug is
administered repeatedly and then suddenly no
longer taken.
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Principles of Pharmacology
Placebo Effects
Placebo:
• 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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Sites of Drug Action
Antagonist:
• A drug that opposes or inhibits the effects of a
particular neurotransmitter on the postsynaptic
cell.
Agonist:
• 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.
Receptor 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 principal ligand.
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
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principal ligand.
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Sites of Drug Action
Effects on Receptors
Presynaptic heteroreceptor:
• A receptor located in the membrane of a terminal
button that receives input from another terminal
button by means of an axoaxonic synapse; binds
with the neurotransmitter released by the
presynaptic terminal button.
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Neurotransmitters and Neuromodulators
Acetylcholine
The first transmitter to be discovered.
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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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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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.
Hemicholinium:
• A drug that inhibits the uptake of choline.
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Acetylcholine
Nicotinic receptor:
• An ionotropic acetylcholine receptor that is
stimulated by nicotine and blocked by curare.
Muscarinic receptor:
• A metabotropic acetylcholine receptor that is
stimulated by muscarine and blocked by
atropine.
Atropine:
• A drug that blocks muscarinic acetylcholine
receptors .
Curare:
• A drug that blocks nicotinic acetylcholine
receptors.
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Neurotransmitters and Neuromodulators
Monoamines
Catecholamines
• Dopamine (DA)
• Norepinephrine (NE)
• Epinephrine
Indolamines
• Serotonin (5-HT)
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Monoamines
Monoamine:
• A class of amines that includes indolamines such
as serotonin and catecholamines such as
dopamine, norepinephrine, and epinephrine.
Indolamines
• Serotonin (5-HT)
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Monoamines
Dopamine
Dopamine:
• A neurotransmitter; one of the catecholamine.
• 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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Monoamines
Dopamine
L-Dopa:
• The levorotatory form of DOPA; the precursor of
the catecholamines; often used to treat
Parkinson’s disease because of its as a
dopamine agonist.
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Monoamines
Dopamine
Nigrostriatal 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
movement.
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Monoamines
Dopamine
Mesolimbic 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
reinforcing effects of drugs that are commonly
abused.
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Monoamines
Dopamine
Mesocortical 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, planning, and preparing
strategies for problem solving.
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Monoamines
Dopamine
Parkinson’s Disease:
• A neurological disease characterized by tremors,
rigidity of the limbs, poor balance, and difficulty in
initiating movements; caused by degeneration of
the nigrostriatal system; Parkinson’s disease has
been treated with L-DOPA.
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Monoamines
Dopamine
AMPT:
• A drug that blocks the activity of tyrosine
hydroxylase and thus interferes with the
synthesis of the catecholamines.
Reserpine:
• A drug that interferes with the storage of
monoamines in synaptic vesicles; serves as a
monoamine antagonist.
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Monoamines
Dopamine
Apomorphine:
• A drug that blocks dopamine autoreceptors at low
doses; at high doses blocks postsynaptic
receptors as well.
Methylphenidate:
• A drug that inhibits the reuptake of dopamine;
also known as “Ritalin”; used to treat children
with attention deficit disorder.
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Monoamines
Dopamine
Monoamine oxidase (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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Monoamines
Dopamine
Chlorpromazine:
• A drug that reduces the symptoms of
schizophrenia by blocking dopamine D2
receptors.
Clozapine:
• A drug that reduces the symptoms of
schizophrenia, apparently by blocking dopamine
D4 receptors.
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Monoamines
Norepinephrine (NE)
Norepinephrine is synonymous with noradrenaline.
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 vigilance or
attentiveness to events in the environment.
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Monoamines
Norepinephrine (NE)
Norepinephrine:
• One of the catecholamines; a neurotransmitter
found in the brain and in the sympathetic division
of the autonomic nervous system.
Epinephrine:
• One of the catecholamies; a hormone secreted
by the adrenal medulla; serves as a
neurotransmitter in the brain.
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Neurotransmitters and Neuromodulators
Monoamines
Norepinephrine (NE)
Norepinephrine:
• One of the catecholamines; a neurotransmitter
found in the brain and in the sympathetic division
of the autonomic nervous system.
Epinephrine:
• One of the catecholamies; a hormone secreted
by the adrenal medulla; serves as a
neurotransmitter in the brain.
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Monoamines
Norepinephrine (NE)
Fusaric acid:
• A drug that inhibits the activity of the enzyme
dopamine-ß-hydroxylase and thus blocks the
production of norepinephrine.
Moclobemide:
• A drug that blocks the activity of MAO-A; acts as
a noradrenergic agonist.
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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Monoamines
Norepinephrine (NE)
Axonal varicosity:
• An enlarged region along the length of an axon
that contains synaptic vesicles and releases a
neurotransmitter or neuromodulator. Most
neurons that release norepinephrine use axonal
varicosities instead of terminal buttons as a
method of release.
Clonidine:
• A drug that stimulates presynaptic noadrenergic
α2 receptors and hence acts as an antagonist,
supressing the release of NE.
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Monoamines
Serotonin (5-HT)
Serotonin:
• Serotonin is an indolamine neurotransmitter; also
called 5-hydroxytryptamine (5-HT); thought to
play a role in the regulation of mood, the control
of eating, sleep, dreaming, and arousal; also
thought to be involved in the regulation of pain.
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Monoamines
Serotonin (5-HT)
• PCPA:
A drug that inhibits the activity of tryptophan
hydroxylase and thus interferes with the
synthesis of 5-HT.
• D system:
A system of serotonergic neurons that
originates in the dorsal raphe nucleus; its
axonal fibers are thin, with spindle-shaped
varicosities that do not appear to form
synapses with other
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Monoamines
Serotonin (5-HT)
• M system:
A system of serotonergic neurons that
originates in the median raphe nucleus; is a
axonal fibers are thick and rounded and
appear to form conventional synapses with
other neurons.
• Fluoxetine (Prozac):
A drug that inhibits the reuptake of 5-HT.
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Monoamines
Serotonin (5-HT)
• Fenfluramine:
A drug that stimulates the release of 5-HT;
used as an appetite suppressant.
• LSD:
Lysergic acid diethylamide
This drug produces distortions of visual
perceptions.
A drug that stimulates 5-HT2a receptors.
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Neurotransmitters and Neuromodulators
Amino Acids
The most common amino acid transmitters are:
• Glutamate
• Gamma-amino-butyric acid (GABA)
• Glycine
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Amino Acids
Glutamate
Glutamate:
• An amino acid; the most important excitatory
neurotransmitter in the brain.
NMDA:
• A drug that serves as a noradrenergic and
serotonergic agonist, also known as “ecstasy”;
has excitatory and hallucinogenic effects.
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Amino Acids
Glutamate
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 ionotropic glutamate receptor that controls a
sodium channel; stimulated by AMPA and
blocked by CNQX; the most common glutamate
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Amino Acids
Glutamate
Kainate receptor:
• An ionotropic glutamate receptor that controls a
sodium channel; stimulated by kainic acid and
blocked by CNQX.
Metabotropic glutamate receptor:
• A category of metabotropic receptors sensitive to
glutamate.
AP5:
• A drug that blocks the glutamate binding site on
NMDA receptors
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Amino Acids
Glutamate
Phencyclidine (PCP):
• A drug that binds with the PCP binding site of the
NMDA receptor and serves as an indirect
antagonist of glutamate.
• Behavioral symptoms include altered body
image, feelings of isolation and sadness,
cognitive disorganization, apathy, hostility
euphoria and dreamlike states.
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Amino Acids
GABA
GABA:
• An amino acid; the most important inhibitory
neurotransmitter in the brain and spinal cord.
Allygllycine:
• A drug that inhibits the activity of GAD and thus
blocks the synthesis of GABA.
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Amino Acids
GABA
Muscimol:
• A direct agonist for the GABA binding site on the
GABA receptor.
Bicuculline:
• A direct antagonist for the GABA binding site on
the GABAA receptor.
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Amino Acids
GABA
Benzodiazepine:
• A category of anxiolytic drugs; an indirect agonist
for the GABAA receptor.
Anxiolytic:
• An anxiety-reducing effect.
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Amino Acids
Glycine
Glycine:
• An amino acid; an important inhibitory
neurotransmitter in the lower brain stem and
spinal cord.
Strychnine:
• A direct antagonist for the glycine receptor.
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Neurotransmitters and Neuromodulators
Peptides
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.
Synthesis takes place in the soma and they are
delivered to the terminal buttons by axoplasmic
transport.
Most peptides appear to serve as neuromodulators,
some act as neurotransmitter.
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Peptides
Endogenous opioid:
• A class of peptides secreted by the brain that act
as opiates; drugs that effect opioid receptors
reduce pain.
Enkephalin:
• One of the endogenous opioids.
Naloxone:
• A drug that blocks opioid receptors.
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Lipids
Cannabinoid:
• A lipid; an endogneous ligand for receptors that
bind with THC, the active ingredient in marijuana.
Anandamide:
• A lipid; the endogenous ligand for receptors that
bind with THC, the active ingredient of marijuana.
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Lipids
Adenosine:
• A nucleoside; a combination of ribose and
adenine; serves as a neuromodulator in the
brain.
Caffeine:
• A drug that blocks adenosine receptors.
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Soluble Gases
Nitric oxide (NO):
• A gas produced by cells in the nervous system;
used as a means of communication between
cells.
Nitric oxide synthase:
• The enzyme responsible for production of nitric
oxide.
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