Neurotransmitters

MD 1 – 1
Group 4 B
Dela Rosa, Vanessa
Ducut, Clare
Dula, Jed
Dungao, Cecilia
Esteban, Ina Patrizia
Gaor, Christel Joy
 Learning Objectives
• Define neurotransmitters
• Enumerate and classify the different neurotransmitters
• Interpret the life cycle of a neurotransmitter
• Identify and describe the different kinds of
neurotransmitter receptors
• Determine how a neurotransmitter is metabolized
• Cite examples of drugs that affect the metabolism or
functions of neurotransmitters
• Name the diseases or disorders to which
neurotransmitters are associated with
• Correlate the given cases during the discussion of
neurotransmitters and conclude the diagnosis and
biochemical basis of the psychiatric disorder
 Case Reports

Dr. Madrid, a 1st year resident

physician in the Department of
Psychiatry, is assigned as the
resident on duty in the out-
patient clinic. On that day he
encountered the following cases:
 Case #1
Mr. R, 25 year old, male, was brought to the
hospital in a state of great distress.
He told the doctors that his neighborhood gas
station was really a Martian space ship sent to
Earth to kidnap him. He was valuable to the
Martians, he said, because only he knew the
secret of Earth's weak defenses.
Mr. R knew all of this because when he was at
home he heard the gas station attendants
whispering to one another about the kidnapping
plans. He was very frightened and had to be put
under sedation.
 Case #2
Mr. P, 46 year old, male, always worked very
hard to support his wife and two small daughters.
Then, he began getting quite upset about the
pressures of his job.
Early one morning, his wife awoke to find Mr. P
sitting quietly on the edge of the bed. He would
not respond to any of her questions and seemed
to be unaware of her presence. No amount of
prodding could move him or even get him to
change his position.
After two days of this behavior, Mr. P was
brought to the hospital.
 Case #3
Ms. S was always a bright student in
elementary and high school.
As she approached the last part of her senior
year in high school, her performance dropped
suddenly. When questioned about this, S would
go into a wild giggling fit saying that only girls had
to take schoolwork so seriously. She began to
stay away from school, hiding alone at home
playing with toy automobiles. Finally, she
announced that she herself was made of steel
and was turning into an automobile.
Because of this, her parents brought her to the
hospital.
 Word Bank
Neurons
• Anatomically & physiologically
specialized for communication and
signaling, and these properties are
fundamental to function of the
nervous system
Synapse
• Structure that permits a neuron to
pass an electrical or chemical signal
to another cell
Neuron
Neuron
Synapse
Reference: http://www.csus.edu/indiv/l/loom/preview%2018.htm
Synaptic transmission
Neurotransmitter
criteria
 criteria
1. Substance must be demonstrated to be
present in the presynaptic terminal and
the cell must be able to synthesize the
substance
2. It should be released on depolarization of
the terminal
3. There should be specific receptors for it
on the postsynaptic membrane
4. There must be a mechanism for
terminating the effect of the
neurotransmitter
Neurotransmitter
receptors
Ionotropic receptor
Metabotropic receptor
Neurotransmitter
life cycle
Reference: http://bioserv.fiu.edu/~walterm/b/addicitions/neurotransmitter_processes.jpg
Neurotransmitters
 Neurotransmitters
• Endogenous substances that act as
chemical messengers by transmitting signals
from a neuron to a target cell across a
synapse
• They can be classified according to their
overall activity or biochemistry
 Classification of
Neurotransmitters
• According to Activity:
• Excitatory
• Inhibitory

• According to Biochemistry:
• Small-Molecule Neurotransmitters
• Acetylcholine
• Amino Acids
• Biogenic Amines
• Purines
• Peptides
• Gaseous Transmitters

• *Some neurotransmitters can exert both excitatory and inhibitory effects depending upon the type of receptors that are present
 Excitatory Neurotransmitters

• They exert excitatory effects on the

neurons, thereby, increasing the likelihood
that the neuron will fire an action potential
• Major excitatory neurotransmitters include:
• Glutamate
• Epinephrine
• Norepinephrine
 Inhibitory Neurotransmitters

• They exert inhibitory effects on the neuron,

thereby, decreasing the likelihood that the
neuron will fire an action potential
• Major inhibitory neurotransmitters include:
• GABA
• Glycine
• Serotonin
 Small
molecule
transmitters
 Acetylcholine

• CNS & PNS

• CNS: inhibitory (also in cardiac tissue)
• PNS: major transmitter of the Autonomic
Nervous System
• Cholinergic Receptors
• Muscarinic (Metabolic)
• Nicotinic (Ionotropic)
Acetylcholine metabolism
CHEMICAL SYNAPSE of
Acetylcholine
 Amino acids

• Glutamate
• GABA
• Glycine
 glutamate

• CNS: Major Excitatory

• Metabotropic glutamate receptors
(mGluRs) and Ionotropic receptors
Glutamate metabolism
 GABA

• CNS: Major inhibitory

• Ionotropic & Metabotropic
GABA METABOLISM
https://www.google.com.ph/search?q=serotonin+metabolism&biw=1223&bih=
786&source=lnms&tbm=isch&sa=X&ei=cYCXVcr8GdCLuwS78Bw&ved=0CA
YQ_AUoAQ#tbm=isch&q=gaba+metabolism&imgrc=XkK0yGUrUPHeUM%3A
 glycine

• CNS: Inhibitory
• Ionotropic glycine receptors

Glycine
Glycine metabolism
https://www.google.com.ph/search?q=serotonin+metabolism&biw=1223&bih=786&source=lnms&tbm=isch&sa=X&ei=cYCXVcr8GdCLuwS78Bw&ved=0CAYQ_AUoAQ#tbm=isch
&q=glycine+metabolism&imgrc=Q-RK2HH6GS1g6M%3A
 Biogenic amines

• Dopamine
• Epinephrine
• Norepinephrine
• Serotonin
• Histamine
catecholamines
 dopamine

• CNS: “Reward-motivated behavior” &

motor control (excitatory)
• PNS: Release of several hormones (insulin
from pancreas & norepinephrine from
blood vessels)

Dopamine
 epinephrine

• Adrenergic
• “Fight-or-Flight” Response
• Sympathetic

Epinephrine
 norepinephrine

• Regulates cardiac function

• Functions along with epinephrine in the
“fight-or-flight” response
Catecholamines metabolism
(tyrosine)
 serotonin

• Regulates mood, appetite, sleep,

memory, and learning
Serotonin metabolism
 Serotonin metabolism.
Tryptophan is the precursor for
serotonin synthesis, with
different enzymatic reactions
in plant and animals.
hydroxylation is the rate
limiting step (enzyme
mediated by tryptophan
hydroxylase in animals or
tryptamine hydroxylase in
plants), while decarboxylation
is a rapid conversion by the
aromatic amino acid
decarboxylase (tryptophan
decarboxylase). The catabolic
metabolite of serotonin is 5-
hydroxyindoleacetic acid, via
5-hydroxyindole acetaldehyde
enzymatically converted by the
membrane-bound
mitochondrial flavoprotein
monoamino oxidase. Modified images
from NCBI PubChem Substance Database.

http://www.hindawi.com/journals/tswj/2012/823493/fig2/
http://worldofbiochemistry.blogspot.com/2012_05_01_archive.html
Purines
 Purines

• ATP has the potential to act as a

transmitter or cotransmitter at synapses in
the PNS & CNS.
• Found in all synaptic vesicles and thus is
coreleased in synaptic transmissions
• Once released, ATP is broken down by
ATPases and 5-nucleotidase to adenosine,
which can be taken up by the
presynaptic termiinal
Peptides
 Peptides
• 3-40 amino acid chains
• Released by neurons and act on receptors
throughout the CNS
• Synthesized at the cell body and then transported
to the terminal
• Packaged into large electron-dense vesicles that
are scattered throughout the presynaptic terminal
rather than in small electron-lucent vesicles
docked at the active zone, where small-molecule
transmitters are stored.
• Oxytocin, insulin, vasopressin
 Gas
neurotransmitters
 Gas neurotransmitters
• Newest category
• Neither packaged into synaptic vesicles nor
released by exocytosis.
• Highly permeant and simply diffuse from synaptic
terminals to neighboring cells after synthesis, their
synthesis being triggered by depolarization of the
nerve terminal
• No specific reuptake mechanisms, no enzymatic
destruction. Ended by diffusion or binding to
superoxide anions or various scavenger proteins
• Nitric oxide (inhibitory)
 Drugs/Agents
that can Affect
Neurotransmitters
 DRUGS MECHANISM MAJOR EFFECTS
Sedative-Hypnotic Binds to certain 1. Sedation
Benzodiazepines GABA receptor in 2. Hypnosis
-diazepam, the CNS 3. Anesthesia
prazepam, 4. Anticonvulsant
alprazolam, effects
clorazepate 5. Muscle relaxation
6. Effects on
Barbiturates respiration and
-phenobarbital, cardiovascular
secobarbital, functions
pentobarbital

Newer Hypnotics
-zolpidem, zaleplon,
cimetidine,
eszopiclone
 Substances Change in Effect on
Neurotransmission Neurotransmitter
release or
availability

Nicotine, Alcohol, Increase the number Increased

Opiates of neurotransmitter
Amphetamines, impulses release

Methamphetamines Release Increased

neurotransmitters neurotransmitter
from vesicles with or release
without
impulses

Nicotine Release more Increased

neurotransmitter neurotransmitter
in response to an release
impulse
 Substances Change in Effect on
Neurotransmission Neurotransmitter
release or
availability
Cocaine, Block reuptake More
Amphetamines neurotransmitter
present
in synaptic cleft

Caffeine Block receptor with No change in

another amount of
molecule neurotransmitter
released or
neurotransmitter
cannot bind
to its receptor on
post synaptic
neuron
 Diseases
Associated with
Neurotransmitters
NEUROTRANSMITTE PHYSIOLOGIC RELATIONSHIP TO
R EFFECTS MENTAL DISORDERS

Acetylcholine • Sleep/wake cycle • Decreased in Alzheimer’s

• Signals muscles to and Parkinson’s disease
become active

Dopamine • Controls complex • Increased in

movements, cognition, Schizophrenia and Mania
motivations, and pleasure • Decreased in Parkinson’s
• Regulates emotional and depression
responses

Norepinephrine • Affects attention, • Increased in

learning, memory, and Schizophrenia, Mania,
regulation of mood, and anxiety
sleep, and wakefulness • Decreased in depression
 NEUROTRANSMITTE PHYSIOLOGIC
R EFFECTS
Serotonin • Affects sleep and
wakefulness, especially
falling asleep
• Affects mood and
thought processes
Gamma-aminobutyric acid • Amino acid that
(GABA) modulates other
neurotransmitters
Reference: http://wps.prenhall.com/wps/media/objects/3020/3092719/toolbox/ch47/Tab47_01.pdf
RELATIONSHIP TO
MENTAL DISORDERS
• Decreased in depression
• Probably plays a role in
thought disorders of
schizophrenia
• Possibly decreased in
anxiety and obsessive-
compulsive disorder
(OCD)
• Decreased in anxiety and
Schizophrenia
 Case study:
schizophrenia
https://www.google.com.ph/search?q=acetylcholine&biw=1223&bih=786&source=lnms&tbm=isch&sa=X&ei=nXeXVaDlFtG2uAT0-
bDQDw&ved=0CAYQ_AUoAQ#tbm=isch&q=schizophrenia&imgrc=jkuy6RSm8S3YKM%3A
https://www.google.com.ph/search?q=acetylcholine&biw=1223&bih=786&source=lnms&tbm=isch&sa=X&ei=nXeXVaDlFtG2uAT0-
bDQDw&ved=0CAYQ_AUoAQ#tbm=isch&q=schizophrenia&imgrc=r6VLTZFjTXw59M%3A
https://www.google.com.ph/search?q=acetylcholine&biw=1223&bih=786&source=lnms&tbm=isch&sa=X&ei=nXeXVaDlFtG2uAT0-
bDQDw&ved=0CAYQ_AUoAQ#tbm=isch&q=schizophrenia&imgrc=rMK-_83PdPCqAM%3A
https://www.google.com.ph/search?q=acetylcholine&biw=1223&bih=786&source=lnms&tbm=isch&sa=X&ei=nXeXVaDlFtG2uAT0-
bDQDw&ved=0CAYQ_AUoAQ#tbm=isch&q=schizophrenia&imgrc=lryHB7UF0f10QM%3A
Case Study: Schizophrenia

• Excessive dopamine synapses Excessive

dopamine receptors
• Blocked glutamate receptors
• Treatment: Antipsychotic drugs
• Class of disorders that are marked by disturbances
of:
• Perception
• Cognition
• Emotions
• Motor behaviors
https://www.google.com.ph/search?q=acetylcholine&biw=1223&bih=786&source=lnms&tbm=isch&sa=X&ei=nXeXVaDlFtG2uAT0-
bDQDw&ved=0CAYQ_AUoAQ#tbm=isch&q=schizophrenia&imgrc=P6kUq6Hj8MJ7IM%3A
 Paranoid-type

• Delusions and auditory hallucinations but

relatively normal intellectual functioning and
expression of emotions characterize this type.
The delusions can often be about being
persecuted by a person or an organization, or
feeling harassed or treated unfairly.
• People with paranoid-types schizophrenia can
exhibit anger, aloofness, anxiety, and can be
argumentative.
 Disorganized-type
• This is characterized by speech and behavior
that are disorganized or difficult to
understand, and flattening or inappropriate
emotions.
• People with disorganized-type schizophrenia
may laugh inappropriately for no apparent
reason, make illogical statements, or seem
preoccupied with their own thoughts or
perceptions. Their disorganized behavior may
disrupt normal activities, such as showering,
dressing, and preparing meals.
 Catatonic-type
• This is characterized by exhibiting extreme ends of the
spectrum. At one end of the extreme the patient cannot
speak, move or respond – there is a dramatic reduction in
activity where virtually all movement stops, as in a catatonic
stupor.
• At the other end of the extreme they are overexcited or
hyperactive, sometimes mimicking sounds (echolalia) or
movements (echopraxia) around them – often referred to
as catatonic excitement.
• Patients may also present other disturbances of movement –
seemingly purposeless actions are performed repetitively
(stereotypic behavior), sometimes to the exclusion of
involvement in any creative of productive activity.
 Undifferentiated-type

• This is characterized by some symptoms

seen in all of the above types, but not
enough of any one of them to define it as
another particular type of schizophrenia.
 Residual-type

• This characterized by a past history of at least

one episode of schizophrenia, but the person
currently has no "positive" symptoms (such as
delusions, hallucinations, disorganized speech,
or behavior).
• It may represent a transition between a full-
blown episode and complete remission, or it
may continue for years without any further
psychotic episodes.
 Symptoms
• Positive symptoms
Hearing voices, suspiciousness, feeling as though they are
under constant surveillance, delusions, or making up words
without a meaning (neologisms).

• Negative (or deficit) symptoms

Social withdrawal, difficulty in expressing emotions (in extreme
cases called a flat affect), difficulty in taking care of
themselves, inability to feel pleasure.
These symptoms cause severe impairment and are often
mistaken for laziness.
 Symptoms
• Cognitive symptoms
Difficulties attending to and processing of information,
understanding the environment, and remembering simple
tasks.

• Affective (or mood) symptoms

Most notably depression, accounting for a very high rate of
attempted suicide in people suffering from schizophrenia.
Anxiety can also be present and may be a direct result of the
psychosis or come and go during a psychotic episode.
 Case correlation #1
• Mr. R, 25 year old, male, was brought to the
hospital in a state of great distress.
• He told the doctors that his neighborhood gas
station was really a Martian space ship sent to
Earth to kidnap him. He was valuable to the
Martians, he said, because only he knew the secret
of Earth's weak defenses.
• Mr. R knew all of this because when he was at
home he heard the gas station attendants
whispering to one another about the kidnapping
plans. He was very frightened and had to be put
under sedation.
 Diagnosis: paranoid
schizophrenia
• Delusions
• Persecutory delusion
• Delusion of grandeur
• Ideas of reference

• Auditory Hallucinations
• Heard the gas attendants whispering about
the kidnapping plans
 Case correlation #2
• Mr. P, 46 year old, male, always worked very hard
to support his wife and two small daughters. Then,
he began getting quite upset about the pressures
of his job.
• Early one morning, his wife awoke to find Mr. P
sitting quietly on the edge of the bed. He would
not respond to any of her questions and seemed to
be unaware of her presence. No amount of
prodding could move him or even get him to
change his position.
• After two days of this behavior, Mr. M was brought
to the hospital.
 Diagnosis: catatonic
schizophrenia
• Extreme of the spectrum
• Won’t move (catatonic stupor)
• Flat affect
• Exclusion of involvement in any productive
activity
 Correlated case #3
• Ms. S was always a bright student in elementary and high
school.
• As she approached the last part of her senior year in high
school, her performance dropped suddenly. When
questioned about this, S would go into a wild giggling fit
saying that only girls had to take schoolwork so seriously.
She began to stay away from school, hiding alone at
home playing with toy automobiles. Finally, she announced
that she herself was made of steel and was turning into an
automobile.
• Because of this, her parents brought her to the hospital.
 Diagnosis: disorganized
schizophrenia
• Inappropriate emotions
• Illogical statement
• Preoccupied with her own thoughts or
perceptions
• Disrupted normal activities
 References
• Katzung, B.G. (editor) : Basic and Clinical
Pharmacology, 12th ed. McGraw-Hills
Companies, Inc. 2012
• Koeppen, B.M. and Stanton, B. A. (editors):
Berne and Levy Physiology, 6th ed. Mosby
Elsevier Inc. 2010
• http://www.livestrong.com/article/155607-
biochemical-causes-of-schizophrenia/
• http://www.webmd.com/schizophrenia/guide
/schizophrenia-types
 VIDEO URLs

• https://www.youtube.com/watch?v=6qS8
3wD29PY
• https://www.youtube.com/watch?v=Who
wH0kb7n0
• https://www.youtube.com/watch?v=bCb
6sjkAdIg