copyright © 2004 allyn and bacon 1 chapter 4 psychopharmacology this multimedia product and its...
Post on 20-Dec-2015
213 views
TRANSCRIPT
1Copyright © 2004 Allyn and Bacon
Chapter 4
Psychopharmacology
This multimedia product and its contents are protected under copyright law.The following are prohibited by law:• any public performance or display, including transmission of any image over a network;•preparation of any derivative work, including the extraction, in whole or in part, of any images;•any rental, lease, or lending of the program.
2Copyright © 2004 Allyn and Bacon
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.
3Copyright © 2004 Allyn and Bacon
Principles of Psychopharmacology Pharmacokinetics
Pharmacokinetics:• The process by which drugs are absorbed,
distributed within the body, metabolized, and excreted.
4Copyright © 2004 Allyn and Bacon
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.
5Copyright © 2004 Allyn and Bacon
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.
6Copyright © 2004 Allyn and Bacon
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.
8Copyright © 2004 Allyn and Bacon
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.
9Copyright © 2004 Allyn and Bacon
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.
10Copyright © 2004 Allyn and Bacon
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.
13Copyright © 2004 Allyn and Bacon
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.
14Copyright © 2004 Allyn and Bacon
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.
15Copyright © 2004 Allyn and Bacon
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.
16Copyright © 2004 Allyn and Bacon
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.
17Copyright © 2004 Allyn and Bacon
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.
18Copyright © 2004 Allyn and Bacon
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.
19Copyright © 2004 Allyn and Bacon
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 principal ligand.
22Copyright © 2004 Allyn and Bacon
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.
24Copyright © 2004 Allyn and Bacon
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.
25Copyright © 2004 Allyn and Bacon
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.
26Copyright © 2004 Allyn and Bacon
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.
27Copyright © 2004 Allyn and Bacon
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.
31Copyright © 2004 Allyn and Bacon
Neurotransmitters and Neuromodulators Monoamines
Catecholamines• Dopamine (DA)• Norepinephrine (NE)• Epinephrine
Indolamines• Serotonin (5-HT)
32Copyright © 2004 Allyn and Bacon
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)
33Copyright © 2004 Allyn and Bacon
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.
34Copyright © 2004 Allyn and Bacon
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.
35Copyright © 2004 Allyn and Bacon
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.
36Copyright © 2004 Allyn and Bacon
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.
37Copyright © 2004 Allyn and Bacon
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.
40Copyright © 2004 Allyn and Bacon
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.
41Copyright © 2004 Allyn and Bacon
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.
42Copyright © 2004 Allyn and Bacon
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.
43Copyright © 2004 Allyn and Bacon
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.
44Copyright © 2004 Allyn and Bacon
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.
45Copyright © 2004 Allyn and Bacon
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.
46Copyright © 2004 Allyn and Bacon
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.
47Copyright © 2004 Allyn and Bacon
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.
48Copyright © 2004 Allyn and Bacon
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.
49Copyright © 2004 Allyn and Bacon
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.
51Copyright © 2004 Allyn and Bacon
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.
52Copyright © 2004 Allyn and Bacon
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 neurons.
53Copyright © 2004 Allyn and Bacon
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.
54Copyright © 2004 Allyn and Bacon
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.
57Copyright © 2004 Allyn and Bacon
Neurotransmitters and Neuromodulators Amino Acids
The most common amino acid transmitters are:
• Glutamate
• Gamma-amino-butyric acid (GABA)
• Glycine
58Copyright © 2004 Allyn and Bacon
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.
59Copyright © 2004 Allyn and Bacon
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 receptor.
61Copyright © 2004 Allyn and Bacon
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
62Copyright © 2004 Allyn and Bacon
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.
63Copyright © 2004 Allyn and Bacon
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.
64Copyright © 2004 Allyn and Bacon
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.
66Copyright © 2004 Allyn and Bacon
Neurotransmitters and Neuromodulators Amino Acids GABA
Benzodiazepine:• A category of anxiolytic drugs; an indirect agonist
for the GABAA receptor.
Anxiolytic:
• An anxiety-reducing effect.
67Copyright © 2004 Allyn and Bacon
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.
68Copyright © 2004 Allyn and Bacon
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.
69Copyright © 2004 Allyn and Bacon
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.
70Copyright © 2004 Allyn and Bacon
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.
71Copyright © 2004 Allyn and Bacon
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.