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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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Principles of Pharmacology
 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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Principles of Pharmacology
 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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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.
 Hemicholinium:
• A drug that inhibits the uptake of choline.
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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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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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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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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.
 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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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. 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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Neurotransmitters and Neuromodulators
 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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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.
• 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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receptor.
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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 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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Neurotransmitters and Neuromodulators
 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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