Psychopharmacology: Chapter 4

Chapter
4
Majority of illustra3ons in this presenta3on are from Biological Psychology
4th edi3on (© Sinuer Publica3ons)
Psychopharmacology
1. Pharmacology comes from a classical Greek word
pharmakon, meaning poison in modern Greek it
means drug. Logus of course means study.
2. Psychopharmacology is an interdisciplinary field
combining psychology with pharmacology and
dealing largely with psychotropic drugs,
neurohormones, and neurotransmiHers (NTs).
Drugs
The term drug has many meanings:
a. Medica3on to treat a disease.
b. A chemical that can be abused.
c. An exogenous chemical that significantly alters
the func3on of certain bodily cells when taken
in rela3vely low doses (chemical that is NOT
required for normal cellular func3oning).
1
NeurotransmiHers
Likewise neurotransmiHers can mean:
a. Special endogenous chemicals (NTs) released in
the brain or glands.
b. When these chemicals are exogenously induced
as drugs they alter brain and behavior.
c. are neurotransmiHers.
d.  Where NTs have widespread effect, drugs have
localized effect in the brain.
Criteria for NTs

1.  Substance must exist in the presynap3c terminals.
2.  Enzymes for synthesis are
present in the terminals or
cell body.
3.  Nerve impulse (ac3on
poten3al) releases
significant amounts of the
substance.
4.  Substance binds to receptors on the postsynap3c
cell.
5
Criteria for NTs

5. Experimental applica3on of the substance
produces changes in the postsynap3c cell.
6. Blocking substance makes
nerve impulse ineffectual
for postsynap3c cell.
2
Kinds of NTs
NeurotransmiHer
Amines Amino Acid Neuropep3des Pep3de Hormones Gases
Quaternary Amines Mono Amines
Acetylcholine
Catecholamines Indolamines
Norepinephrine Epinephrine
Dopamine Serotonin 7
Kinds of NTs

NeurotransmiHer
Histamine
Gamma-‐aminobutyric Acid (GABA)
Glycine
Glutamate
Kinds of NTs

NeurotransmiHer
Met-‐enkephalin Dynorphin A
β-‐endorphin
Leu-‐enkephalin
3
Kinds of NTs
NeurotransmiHer
Neuropep3de Y
Oxytocin
Substance P
Cholecystokinin (CCK) Hypothalamic Releasing Hormones
Vasopressin
10
Kinds of NTs

NeurotransmiHer
Nitric Oxide (NO)
Carbon Monoxide (CO)
11
NTs and Receptors

NeurotransmiHers can bind to ionotropic and
metabotropic receptors in a variety of ways
opening or closing them like keys.
12
4
Agonists
Agonists are chemicals that mimic NT behavior.
These can bind to receptors and cause similar
effects produced by NTs.
13
Antagonists
Agonists are chemicals that work opposite to NTs.
These can bind to receptors blocking or
deac3va3ng them.
14
Acetylcholine
1.  Acetylcholine (ACh) was first iden3fied by Henry
Dale in 1914 and was confirmed as a by OHo
Loewi, (1938) through a dream (1921) as a
neurotransmiHer, he called
vagusstoff (from vagus nerve).
OHo Loewi 15
5
Vagusstoff
2. OHo Loewi’s determina3on of vagusstoff was
made in the cardiac muscle of the frog. And
supported the idea of this chemical release at
the synap3c clef.
16
ACh and NS

3.  This vagusstoff or acetylcholine was not only
found in PNS but also CNS of many organisms
including humans.
4.  Acetylcholine is used in ANS (autonomic ganglia)
and the only neurotransmiHer used in the
motor division of the soma3c nervous system.
5.  Acetylcholine was extensively studied at the
neuromuscular junc3on (NMJ).
17
ACh and Brain

6. Acetylcholine neurons are found in dorsolateral
pons, medial septum, & basal forebrain. Its
release in brain results in facilitatory effects. And
this NT is involved with learning and
memory in the CNS.
18
6
Myasthenia Gravis
Deple3on of ACh in the PNS leads to a number of
muscular problems, like Myasthenia Gravis in which
the pa3ent suffers from dropping eyelid. When Ach
is increased the condi3on is ameliorated.
en.wikipedia.org
When an intravenous injec3on of edrophonium chloride or
neos3gmine is given it reverses eye dropping, by breaking down
Acetylcholinesterase (AChE) and increasing ACh. 19
Alzheimer’s Disease
1.  Reduc3on of ACh in the CNS is implicated in
Alzheimer’s disease affec3ng memory and other
func3ons.
2.  In this disease Choline acetyltransferase (ChAT)
an enzyme is less ac3ve and does not assist in
ACh synthesis in the terminal vesicles.
3.  Drugs or enzymes
that boost ACh improve
hHp://www.nature.com
hHp://www.rnw.nl
Alzheimer pa3ents.
20
ACh Receptors
1.  ACh ionotropic receptor consists of five
subunits. And can be bound by agonists like
nico3ne and muscarine
2.  These are fast ac3ng ligand-‐gated receptors and
open channels for Na+ ions.
3.  Most ACh receptors are found in NMJ
autonomic ganglia
and some in CNS.
www.scholarpedia.org
21
7
ACh and Agonists
A number of ACh agonists and antagonists have
been studied in detail. Among these agonists
nico3ne (tobacco) and muscarine (mushrooms)
mimic ACh-‐like responses.
Acetylcholine Nico3ne Muscarine

www.tobaccoworld.org
www.healthline.com
22
Tobacco Mushrooms
Nico3ne Effects
1.  Nico3ne is a s3mulant and increases blood
pressure, secre3on of hydrochloric acid in the
stomach and motor ac3vity of the bowels.
2.  It binds to ACh receptors, and opens up Na+
channels increasing ac3vity in the muscles
through PNS.
23
Muscarinic Effects
1.  There are five different kinds of of ACh
metabotropic (muscarinic) receptors (M1-‐5) and
are thus slower than nACh receptors.
2.  These are found in heart, smooth muscle and
CNS.
24
8
Nico3ne & Muscarine Antagonists
1.  Curare (d-‐tubocurarine) block nACh receptors
thus act like antagonists.
2.  Atropine and scopolamine are muscarine
antagonists.
en.wikipedia.org
en.wikipedia.org
Curare Atropine 25
ACh Inac3va3on & Facilita3on

1.  ACh can be inac3vated by blocking Choline
reuptake mechanism by Hemicholium.
2.  ACh release is also blocked by botulinum toxin
(Botox). Botox blocks ACh release, muscle
contrac3ons and wrinkles.
3.  ACh release is facilitated by black widow spider
venom (muscle spasms) and Neos3gmine. They
both interfere with AChE ac3vity.
26
Black Widow Spider
Monoamines
Catecholamines consist of dopamine (DA),
norepinephrine (NE), and epinephrine (EPI), and
Indolamines include serotonin (5-‐HT) and
melatonin they all share chemical structure.
www.sciencephoto.com
www.3dchem.com
www.3dchem.com
Dopamine Norepinephrine Epinephrine

www.3dchem.com
www.3dchem.com
27
Serotonin Melatonin
9
Dopamine
1.  Over one million neurons in the brain contain
DA, this number is extremely small, however DA
plays a major role in severe disorders like
schizophrenia and Parkinson’s disease.
2.  Dopamine neurons contain several types of DA
receptors (DA1-‐5).
3.  Drugs can affect DA receptors differently.
Affinity of an3psycho3c drug haloperidol is
twice to DA2 than DA1, thus relieves
schizophrenic symptoms. 28
Dopamine
4.  In the brain there are two systems that regulate
DA ac3vity. One is mesostriatal system which
projects from the substan3a nigra to the
caudate nucleus and putamen, and is implicated
in Parkinson’s disease.
5.  A disease marked with
res3ng tremors to complete
paralysis. The condi3on
ameliorated with L-‐dopa.
29
Dopamine
6. The second system is called the mesolimbic
system that projects from ventral tegmental
area to the limbic system. Over ac3vity of this
pathway is implicated in schizophrenia.
30
10
Norepinephrine
1.  The locus coeruleus (LC) gives rise to NE fiber
system that connects to spinal cord, cerebellum,
brain stem, thalamus, amygdala, and basal
cerebrum.
2.  Norepinephrine is
synthesized from dopamine
within vesicles and is
secreted from varicosi3es of
LC along fibers.
31
Norepinephrine
3.  Norepinephrine will increase from LC during
stress and will alter cogni3ve func3on engaging
prefrontal cortex to increase mo3va3on.
4.  Animal models of LC destruc3on
and reduc3on in NE suggests
its important role in
Alzheimer’s disease.
5.  Norepinephrine release from
LC is related to REM
sleep. 32
Serotonin
1.  Serotonin (5-‐HT) cells are mostly located in the
gut (98%) with only 2% in the brain.
2.  Serotonin cell bodies are located in brainstem
raphe nuclei and project to cortex.
3.  Serotonin regulates
moods, anxiety and
arousal.
4.  Serotonin and NE are
implicated in bipolar and
other mood disorders. 33
11
Glutamate
1.  Glutamate (and aspartate) are two excitatory
neurotransmiHers in the brain.
2.  Glutamate binds to many ionotropic receptors
like α-‐amino-‐3-‐hydroxy-‐5-‐methyl-‐4-‐isoxazole-‐
propionic acid (AMPA), N-‐methyl-‐D-‐aspartate
(NMDA), kinate and a few metabotropic
receptors.
www.mpoullis.net
34
Glutamic Acid
Glutamate
3.  Glutamate can cause excitotoxicity killing
neurons. Astrocytes clear glutamate from the
clef to save neurons.
4.  Interest in glutamate, was greatly increased due
its implica3on in memory and long-‐term
poten3a3ng (LTP).
35
Glutamate Ac3on
5. Glutamate (ligand) binds to NMDA receptors when
depolariza3on is below 35 mv. This makes NMDA
receptors ligand-‐gated and voltage sensi3ve.
Increase in intracellular Ca2+ increase Na+ flux.
36
12
γ-‐amino butyric acid (GABA)
1.  Unlike glutamate, GABA (and Glycine) is an
inhibitory NT. There are three classes of GABA
receptors (GABAA-‐C). GABAA and GABAC are
ionotropic and GABAB is metabotropic receptor.
www.cybermedicine2000.com
www.cybermedicine2000.com
37
GABAA Molecule Glycine Molecule
GABA
2.  Binding of GABA to its receptor opens up
channel to let Cl-‐ ions to enter the neuron
causing hyperpolariza3on.
3.  It is GABA that blocks many excitatory responses
in the brain resis3ng seizures. Drugs that block
GABA can produce seizures.
38
Neuropep3des, Pep3des & Gases

1.  Opioid pep3des (met-‐enkephalin, leu-‐
enkephalin, β-‐endorphin and dynorphin) mimic
opiate drugs like morphine.
2.  Many other pep3des (substance P, neurotensin,
cholecytokinin [CCK], neuropep3de Y,
vasopressin, oxytosin) act like NTs and
hormones.
3.  Finally gases like nitric oxide (NO) and carbon
monoxide (CO) act like NTs in neurons.
39
13
Neuropsychopharmacology
1.  Neuropsychopharmacology is rapidly
developing, field of drugs related to altering
behavior. Drugs are extracted from natural
sources (plants etc.) or synthesized from
ar3ficial means (man-‐made).
2.  Most of these drugs
interact with specific receptors,
unlike neurotransmiHers that
interact with all receptors.
40
Drug-‐Receptor Affinity
The degree of chemical aHrac3on between a ligand
and a receptor is termed as binding affinity. Some
drugs bind to receptors more strongly than others.
41
Drug Efficacy
Propensity of a ligand (drug) to ac3vate a receptor
is called efficacy. Some drugs (agonists) have high
efficacy than others.
42
14
Dose-‐Response Curve
Dose-‐response curve is a rela3onship between drug
dose and observed effect. Low dosage is ineffectual
and high dose lethal. Effec3ve dosage (ED50) is half
maximal response.
43
Drug Tes3ng
1.  Dose-‐response curves can be used to assess
different drugs. Effec3ve dosage (ED50) of Drug
A is lower than drug B (Lef Figure).
2.  Drug A will bind more than drug B (Right Figure).
44
Drug Dose Range

Every drug at some dosage level becomes lethal.
The wider the range a drug has between effec3ve
ED50 and lethal dosage (LD50 ), the safer the drug is.
Drug represented by blue curves, is safer than one
shown by yellow curves.
45
15
Drug Tolerance
1.  Repeated use of a drug leads to tolerance.
Metabolic tolerance is a biochemical tolerance
that increases the metabolites such that they
become less effec3ve. Liver generally eliminates
such metabolites before tolerance occurs.
2.  Func3onal tolerance leads to down-‐regula3ng
receptors in the target neurons if an
agonist con3nues to occupy
neuronal environment.
46
Other Drug Effects

1.  Cross Tolerance: Tolerance to one drug that
generalizes to other drugs.
2.  Sensi3za3on: Drug craving caused by changes in
the brain and receptor up regula3on.
3.  Withdrawal Symptoms: Unpleasant
cogni3ve sensa3on associated with
drug cessa3on.
47
Drug Administra3on
48
16
Drugs Affec3ng Presynap3c Sites
1.  Synthesis of transmiHers is inhibited (enzymes)
at the axon.
2.  Axonal transport is impaired (microtubles) by
Colchicine.
3.  Ac3on poten3als are blocked by tetrodotoxin.
49

4.  Reserpine inhibits uptake of transmiHers into
vesicles.
5.  Ca++ channel blockers (verapamil) inhibit NT
release.
6.  Modula3on (caffeine) of transmiHer release by
presynap3c receptor.
50

7.  Inac3va3on (amphetamine) of transmiHer
reuptake thus prolonging synap3c ac3vity.
8.  Blockade of transmiHer degrada3on. MAOIs
block enzymes that degrade NTs. Thus NT
prolongs at the synapse.
51
17
Drugs Affec3ng Postsynap3c Sites
1.  Inac3va3on of enzyme in the clef to prolong
transmiHer ac3vity.
2.  Altera3on (alcohol) of postsynap3c receptors
(GABA) to increase inhibi3on.
3.  Blockade (curare) of nAChrs.
52
Drugs Affec3ng Postsynap3c Sites

4.  Ac3va3on (nico3ne) ac3vates ACh receptors.
5.  Ac3va3on (lithium) of second messengers cyclic
AMP.
53
Classes of Drugs (Analgesics)

1.  Poppy flowers produce opium. Opium contains
morphine, a powerful pain-‐killer (analgesic) and
is addic3ve. Likewise heroin (ar3ficial form of
morphine) is also analgesic and addic3ve.
2.  Hughes and Kosterlitz (1975) iden3fied two
pep3des that bound to opioid
receptors and called them
enkephalins. Enkephalins like
morphine relieved pain and
were addic3ve.
Poppy Flowers 54
18
Analgesics: Opiates
3.  Other endogenous morphine (endorphins) and
dynorphin were also discovered that were
endogenous to the brain.
4.  Pert and Snyder (1973) discovered
opiate receptors in the limbic
system, hypothalamus, locus
coeruleus, and periaqueductal
gray. Morphine bound to
receptors in these regions.
55
Analgesics: Cannabinoids
1.  The second class of analgesics is based on
tetrahydrocannabinol (THC) main ingrediant in
marijuana and hashish extracted the cannabis
plant.
2.  In 1992 an endogenous
cannabanoid ligand was
discovered (anandamide).
3.  Cannabanoid receptors are found
in substan3a nigra, hippocampus,
cerebellum and the cortex. 56
Depressants
1.  Throughout human history alcohol has been the
easiest drug to concoct. It is a tension reducer.
2.  Alcohol has a biphasic effect on the brain. An
ini3al s3mula3ng phase and longer depressant
phase later on.
3.  Prolonged usage of alcohol damages nerve cells.
Purkinje cells (cerebellum), pyramidal neurons
(hippocampus) show such damage. Thus motor
and memory losses over the pa3ent’s life3me.
57
19
Depressants
4.  Alcoholism and dietary deficiency (thiamine)
leads to Korsakoff’s syndrome.
5.  Low dosage of alcohol s3mulate dopamine
pathways (euphoria) and perhaps opiate
receptors in numbing pain.
6.  Alcohol’s depressive effect is because of its
interac3on with GABAA receptors which are
involved with inhibi3on in the brain.
58
Depressants
7. Abs3nence from alcohol leads to brain recovery
in gray maHer (cortex) and reduc3on in lateral
ventricular volume.
59
Anxioly3cs
1.  Anxioly3cs (Anxiety and Greek ly8cos “able to
loosen”) are drugs ameliorate disabling
emo3onal distress, like fear and terror.
2.  Benzodiazepines (Valium etc.)
are anxioly3c and enhance
GABA receptors ac3vity to
increase inhibi3on.
3.  Hormone allopregnanolone
suspected to be endogenous
anxioly3c is increased by alcohol. 60
20
S3mulants
1.  Nico3ne: Found largely in tobacco s3mulates
nico3nic receptors at the neuromuscular
junc3ons (NMJ). Also in the CNS.
2.  Cocaine: Derived from coca leaves is used as a
local anesthe3c and also relieves depression.
Increases dopamine in the synapse.
3.  Amphetamines: Causes heightened alertness,
and even euphoria and wards off boredom.
61
Hallucinogens
1.  Lysergic Acid Diethylamide (LSD):
•  Potent drug that causes hallucina3ons was
discovered in 1938 by Hoffmann.
•  In the 1950s scien3sts thought that it would
provide a model for psychosis.
•  Why LSD causes hallucina3ons is not
understood?
•  Former users report flashbacks resembling
hallucina3ons. Memory or plas3c changes?
62
Hallucinogens
2. Phencyclidine (PCP):
•  Also called angel dust, is a potent analgesic
and anesthe3c.
•  Dropped from use because of side effects
(delirium, disorganized percep3on, hos3lity
etc).
•  Toxic reac3ons (four Cs) comba3veness,
catatonia, convulsions (or coma), confusion.
•  May provide useful model of schizophrenia.
63
21
Hallucinogens
3. Peyote and Mushrooms:
•  Peyote seed and mushrooms can alter states
of consciousness resembling hallucina3ons.
Fewer side effects.
•  Eminent scien3sts advocated their use.
Carlos Castaneda Mushroom Timothy Leary
64
Recrea3onal Drugs
All drugs used in recrea3onal form have
devasta3ng effects on the brain. Drugs like Ecstasy,
hallucinogenic amphetamine can reduce serotonin
axons in the brain within a single dose.
65
Drug Abuse
Any comprehensive model of drug abuse should be
able to answer the following ques3ons.
1.  What social and environmental factors lead the
individual to start abusing the drug?
2.  What factors make her con3nue?
3.  What physiological factors makes a substance
rewarding?
4.  What is addic3on in behavioral and physiological
terms, and why it is so hard to quit?
66
22
Drug Models
1.  The Moral Model: The abuser lacks morals and
thus self-‐control. Train self-‐control
(punishment?).
2.  The Disease Model: Drug abuser is diseased
thus needs the drug. Needs treatment rather
than moral punishment.
3.  The Physical Dependence Model: Drugs are
con3nued because their cessa3on cause
unpleasant withdrawal symptoms.
67
Drug Models
4. The Posi3ve Reward Model: Proposes animals
and humans engage in drug ac3vity for its
reward-‐like consequences.
68
Individual Differences
Individuals differ in their suscep3bility to be
becoming drug addicts because of many factors.
1.  Biological Factors: men are more likely to abuse
drugs than women.
2.  Family Situa3on: Family breakup, poor parental
rela3onships, an3social siblings lead to drug abuse.
3.  Personal Characteris3cs: Aggressiveness and poor
emo3onal leads to drug abuse.
4.  Environmental Factors: Prevalence of drug use in
community.
69
23
Drug Abuse Preven3on & Treatment
1.  Detoxifica3on: Drugs like benzodiazepines

reduce early withdrawal symptoms of drug
abusers.
2.  Agonists: Agonists can wean the individual form
drugs, e.g., methadone reduces heroin appe3te.
3.  An3craving Medica3ons: Drugs that reduce
appe3te for the abused substance, e.g.,
naltrexone reduces alcohol pleasure.
70
Drug Abuse Preven3on & Treatment
4. Immuniza3ons: Trigger the immune system to

produce an3bodies that remove targeted drugs
from circula3on.
71
24

Psychopharmacology: Chapter 4

Încărcat de

Informații document

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

Psychopharmacology: Chapter 4

Încărcat de

Drepturi de autor:

Formate disponibile

Chapter

Criteria for NTs

Criteria for NTs

Amines Amino Acid Neuropep3des Pep3de Hormones Gases

Quaternary Amines Mono Amines

Kinds of NTs

Amines Amino Acid Neuropep3des Pep3de Hormones Gases

Kinds of NTs

Amines Amino Acid Neuropep3des Pep3de Hormones Gases

Amines Amino Acid Neuropep3des Pep3de Hormones Gases

Cholecystokinin (CCK) Hypothalamic Releasing Hormones

Kinds of NTs

Amines Amino Acid Neuropep3des Pep3de Hormones Gases

Nitric Oxide (NO)

Carbon Monoxide (CO)

NTs and Receptors

ACh and NS

ACh and Brain

Acetylcholine Nico3ne Muscarine

ACh Inac3va3on & Facilita3on

Dopamine Norepinephrine Epinephrine

Neuropep3des, Pep3des & Gases

Drug Dose Range

Other Drug Eﬀects

Drugs Aﬀec3ng Presynap3c Sites

Drugs Aﬀec3ng Presynap3c Sites

Drugs Aﬀec3ng Postsynap3c Sites

Classes of Drugs (Analgesics)

Carlos Castaneda Mushroom Timothy Leary

1. Detoxiﬁca3on: Drugs like benzodiazepines

Drug Abuse Preven3on & Treatment

4. Immuniza3ons: Trigger the immune system to

S-ar putea să vă placă și

1.  Detoxiﬁca3on: Drugs like benzodiazepines