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CHAPTER I

ABSTRACT

Neurotransmitters are essential chemical messengers used by neurons in the brain to send

and receive electro-chemical signals within the brain and facilitate communication with all the

other organ systems in the body. These powerful neurochemicals are responsible for regulating

practically all functions in life, such as cognitive and mental performance, sleep cycle, weight,

pain perception and response and our emotional states.

Essentially they are the communication system of the mind, body and nervous system. To

get a good picture in your head of what this means, you can think of your telephone service. A

complex web of interconnections that allows communication to take place. Neurotransmitters

literally govern every system in the body either directly or indirectly.


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CHAPTER II

INTRODUCTION

This paper made for fulfill my task and finished my 3rd

english lesson in Medical faculty

of Trisakti University. On the other hand, me as medical student want to search and understand

every disease and symptom in my country and also in the world, because i will approach all of

that when i become a phsycian.

Neurotransmitters are chemicals located and released in the brain to allow an impulse

from one nerve cell to pass to another nerve cell. There are approximately 50 neurotransmitters

identified. There are billions of nerve cells located in the brain, which do not directly touch each

other. Nerve cells communicate messages by secreting neurotransmitters. Neurotransmitters can

excite or inhibit neurons (nerve cells). Some common neurotransmitters are acetylcholine,

norepinephrine, dopamine, serotonin and gamma aminobutyric acid (GABA). Acetylcholine and

norepinephrine are excitatory neurotransmitters while dopamine, serotonin, and GABA are

inhibitory. Each neurotransmitter can directly or indirectly influence neurons in a specific

portion of the brain, thereby affecting behavior.

Medical researchers tell us that deficiencies, imbalances, disruption or malfunctioning of

neurotransmitters is extremely common in our society and is at the root of many of common

health conditions, because when neurotransmitters are not functioning properly then the mind

and body do not communicate effectively. When communication malfunctions, then organ

systems don't function as they should. This results in a variety of undesirable symptoms both

physically and psychologically. Recent research suggests that approximately eight out of ten

people suffer from some form of neurotransmitter imbalance.
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CHAPTER III

LITERATURE REVIEW

3.1 Definition of Neurotransmitter

Neurotransmitters are essential chemical messengers used by neurons in the brain to send

and receive electro-chemical signals within the brain and facilitate communication with all the

other organ systems in the body. These powerful neurochemicals are responsible for regulating

practically all functions in life, such as cognitive and mental performance, sleep cycle, weight,

pain perception and response and our emotional states.6

Information from one neuron flows to another neuron across a synapse. The synapse is a small

gap separating neurons. The synapse consists of:

a presynaptic ending that contains neurotransmitters, mitochondria and other cell

organelles,

a postsynaptic ending that contains receptor sites for neurotransmitters and, a synaptic cleft or space between the presynaptic and postsynaptic endings. It is about

20nm wide.

An action potential cannot cross the synaptic cleft between neurones. Instead the nerve impulse

is carried by chemicals called neurotransmitters. These chemicals are made by the cell that is

sending the impulse (the pre-synaptic neurone) and stored in synaptic vesicles at the end of the

axon. The cell that is receiving the nerve impulse (the post-synaptic neurone) has chemical-gated


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ion channels in its membrane, called neuroreceptors. These have specific binding sites for the

neurotransmitters. 7

3.2 Mechanism of impulse transmission

1. At the end of the pre-synaptic neurone there are voltage-gated calcium channels. When an

action potential reaches the synapse these channels open, causing calcium ions to flow into the

cell.

2. These calcium ions cause the synaptic vesicles to fuse with the cell membrane, releasing their

contents (the neurotransmitter chemicals) by exocytosis.

3. The neurotransmitters diffuse across the synaptic cleft.

4. The neurotransmitter binds to the neuroreceptors in the post-synaptic membrane, causing the

channels to open. In the example shown these are sodium channels, so sodium ions flow in.


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5. This causes a depolarisation of the post-synaptic cell membrane, which may initiate an action

potential, if the threshold is reached.

6. The neurotransmitter is broken down by a specific enzyme in the synaptic cleft; for example

the enzyme acetylcholinesterase breaks down the neurotransmitter acetylcholine. The

breakdown products are absorbed by the pre-synaptic neurone by endocytosis and used to re-

synthesise more neurotransmitter, using energy from the mitochondria. This stops the synapse

being permanently on.7

3.3 Kinds Of Neurotransmitters

Neurotransmitter Molecules

Neurotransmitters can be broadly split into two groupsthe classical, small molecule

neurotransmitters and the relatively larger neuropeptide neurotransmitters. Within the category

of small molecule neurotransmitters, the biogenic amines (dopamine, noradrenaline, serotonin

and histamine) are often referred to as a discrete group because of their similarity in terms of

their chemical properties.

Small molecule neurotransmitters

Type Neurotransmitter Postsynaptic effect

Acetylcholine Excitatory

Amino acids Gamma aminobutyric acidGABA Inhibitory

Glycine Inhibitory

Glutamate Excitatory

Aspartate Excitatory

Biogenic amines Dopamine Excitatory

Noradrenaline Excitatory

Serotonin Excitatory


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Histamine Excitatory

Neuropeptide neurotransmitters

Corticotropin releasing hormone

Corticotropin (ACTH)

Beta-endorphin

Substance P

Neurotensin

Somatostatin

Bradykinin

Vasopressin

Angiotensin II

3.4 Table of Neurotransmitters1

Transmitter Molecule Derived From Site of Synthesis

Acetylcholine Choline CNS, parasympathetic nerves

Serotonin

5-Hydroxytryptamine (5-HT)Tryptophan CNS, chromaffin cells of the gut, enteric cells

GABA Glutamate CNS

Glutamate CNS

Aspartate CNS

Glycine spinal cord

Histamine Histidine hypothalamus
http://themedicalbiochemistrypage.org/nerves.html#achhttp://themedicalbiochemistrypage.org/nerves.html#5hthttp://themedicalbiochemistrypage.org/nerves.html#gabahttp://themedicalbiochemistrypage.org/nerves.html#gabahttp://themedicalbiochemistrypage.org/nerves.html#5hthttp://themedicalbiochemistrypage.org/nerves.html#ach


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Epinephrine

synthesis pathwayTyrosine adrenal medulla, some CNS cells

Norpinephrine

synthesis pathway

Tyrosine CNS, sympathetic nerves

Dopamine

synthesis pathwayTyrosine CNS

Adenosine ATP CNS, peripheral nerves

ATP sympathetic, sensory and enteric nerves

Nitric oxide, NO Arginine CNS, gastrointestinal tract

3.5 Neurotransmitters Receptors

Neurotransmitters exert their effect by binding to specific receptors on the neuronal

postsynaptic membrane. A neurotransmitter can either excite its neighbouring neuron so

increasing its activity, or inhibit its neighbouring neuron, suppressing its activity. In general,

the activity of a neuron depends on the balance between the number of excitatory and inhibitory

processes affecting it, and these can occur simultaneously. Most neurotransmitter receptors can

be divided into two types ligand-gated receptors and G-protein linked receptors.

Stimulation of a ligand-gated receptor enables a channel in the receptor to open and permits the

influx of chloride and potassium ions into the cell. The positive or negative charges that enter the

cell either excite or inhibit the neuron. Ligands for these receptors include excitatory

neurotransmitters, such as glutamate and, to a lesser extent, aspartate. Binding of these ligands to

the receptor produces an excitatory postsynaptic potential (EPSP). Alternatively, binding of

inhibitory neurotransmitter ligands, such as GABA and glycine, produces an inhibitory

postsynaptic potential (IPSP). These ligand-gated receptors are also known as ionotropic or fast
http://themedicalbiochemistrypage.org/nerves.html#catecholamineshttp://themedicalbiochemistrypage.org/aminoacidderivatives.html#tyrosinehttp://themedicalbiochemistrypage.org/nerves.html#catecholamineshttp://themedicalbiochemistrypage.org/aminoacidderivatives.html#tyrosinehttp://themedicalbiochemistrypage.org/nerves.html#catecholamineshttp://themedicalbiochemistrypage.org/aminoacidderivatives.html#tyrosinehttp://themedicalbiochemistrypage.org/aminoacidderivatives.html#nohttp://themedicalbiochemistrypage.org/aminoacidderivatives.html#nohttp://themedicalbiochemistrypage.org/aminoacidderivatives.html#tyrosinehttp://themedicalbiochemistrypage.org/nerves.html#catecholamineshttp://themedicalbiochemistrypage.org/aminoacidderivatives.html#tyrosinehttp://themedicalbiochemistrypage.org/nerves.html#catecholamineshttp://themedicalbiochemistrypage.org/aminoacidderivatives.html#tyrosinehttp://themedicalbiochemistrypage.org/nerves.html#catecholamines


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receptors.

G-protein linked receptors are indirectly linked to ion channels, via a second messenger system

involving G-proteins and adenylate cyclase. These receptors are neither precisely excitatory nor

inhibitory and modulate the actions of the classic excitatory and inhibitory neurotransmitters

such as glutamate and glycine. These receptors tend to have an inhibitory effect if they are linked

to the Gi protein in the cell membrane, and a more excitatory effect if linked to the Gs protein.

G-protein linked receptors are known as metabotropic or slow receptors and examples include

GABA-B, glutamate, dopamine (D1 and D2), 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A,

5-HT2C receptors.

Serotoning receptors

Type Distribution Postulated Roles

5-HT1 Brain, instetinal nerves Neuronal inhibition, behavioural

effects, cerebral vasoconstriction

5-HT2 Brain, heart, lungs, smooth

muscle control, GI system,

blood vessels, platelets

Neuronal excitation,

vasoconstriction, behavioural

effects, depression, anxiety

5-HT3 Limbic system, ANS Nausea, anxiety

5-HT4 CNS, smooth muscle Neuronal excitation, GI

5-HT5,6, 7

Brain Not known

Noradrenaline receptors


Alpha1 Brain, heart, smooth

muscle

Vasoconstriction, smooth muscle control

Alpha2 Brain, pancreas, smooth

muscle

Vasoconstriction, presynaptic effect in GI

(relaxant)

Beta1 Heart, brain Heart rate (increase)


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Beta2 Lungs, brain, skeletalmuscle

Bronchial relaxation, vasodilatation

Beta3 Postsynaptic effector cells Stimulation of effector cells

Dopamine receptors


D1, 5-like

Brain, smooth muscle Stimulatory, role inschizophrenia?

D2, 3, 4-

like

Brain, cardiovascular system,

presynaptic nerve terminals

Inhibitory, role in

schizphrenia?

Acetylcholine receptors


M1 Nerves CNS excitation, gastric acid

secretion

M2 Heart, nerves, smooth muscle Cardiac inhibition, neural

inhibition

M3 Glands, smooth muscle,

endothelium

Smooth, muscle contraction,

vasodilation

M4 ?CNS? Not known

M5 ?CNS? Not known

NM Skeletal muscles neuromuscularjunction

Neuromuscular transmission

NN Postganglionic cell body dendrites Ganglionic transmission

Co-transmission

Several different neurotransmitters can be released from a single nerve terminal,

including neuropeptides and small molecule neurotransmitters. As well as acting as

neurotransmitters in their own right, neuropeptides can act as co-transmitters. As

co-transmitters, they can activate specific pre- or postsynaptic receptors to alter the


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responsiveness of the neuronal membrane to the action of classical neurotransmitters, such as

noradrenaline and serotonin.

Serotonin, noradrenaline and dopamine are involved in the control of many of our mental states,

sometimes acting on their own and at other times acting together (illustrated in the diagram

below). These and other neurotransmitters are likely to play a pivotal role in the pathological

basis of mental illness and diseases of the brain. Much of the evidence for this stems from the

fact that most of the effective antidepressant drugs are thought to work by changing either

serotonin and/or noradrenaline metabolism, or receptor sensitivity to these neurotransmitters.

Understanding the numerous neurotransmitters, their receptors, locations and interactions

with one another has been central to the design of medicines for mental illness. This acquired

knowledge has led to the development of successful products for many brain disorders including

epilepsy, schizophrenia, Parkinsons disease,depression, anxiety disorders and migraine .


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CHAPTER IV

CORRELATION

4.1 What Causes Neurotransmitter Deficiency, Imbalance or Malfunctioning

1. Alcohol, drugs and nicotine (both prescription and illegal)Many people with neurotransmitter imbalances or deficiencies often turn to alcohol and

drugs to counteract or soothe the symptoms they are having from an already existing

imbalance or deficiency and although initially they provide some relief, they ultimately

damage and deplete neurotransmitters even more. Anyone with neurotransmitter issues is

at extremely high risk of addiction. On the other hand, the use of drugs and alcohol cause

neurotransmitter depletion as they overstimulate them to the point that they stop

producing them.

2. Excessive stressHigh levels of ongoing stress also cause malfunctioning and depletion of

neurotransmitters. This can be the result of a high stress lifestyle that doesn't ease up or

stressful circumstances you must endure like a demanding job, poverty, chronic illness

etc. If you lived with child abuse or neglect as a child, chances are very great that your

neurotransmitters are out of balance and/or deficient.

3. GeneticsSome people are born with deficiencies or malfunctioning neurotransmitters because

they inherit them.


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There are many symptoms as a result of neurotransmitter imbalances or neurotransmitter

deficiency, but these are some of the most common:

Alcoholism and drug addiction, Depression, ADHD/ADD, Anxiety, Impulsive behavior,

Moodiness, Restlessness, Panic attacks, Bipolar disorder, Obsessive-compulsive disorder, Eating

disorders, Insomnia, Poor concentration, Cognitive disorders, Mood swings. 6

4.2Neurotransmitters, mental disorders, and medications1) Schizophrenia

Impairment of dopamine-containing neurons in the brain is implicated in

schizophrenia , a mental disease marked by disturbances in thinking and emotional

reactions2. Neuroimaging studies have demonstrated anatomical abnormalities, such as

enlargement of the ventricles and decreased brain volume in medial temporal areas, in patients

with schizophrenia4. Medications that block dopamine receptors in the brain, such as

chlorpromazine and clozapine , have been used to alleviate the symptoms and help

patients return to a normal social setting.

2) Depression

In depression, which afflicts about 3.5% of the population, there appears to be

abnormal excess or inhibition of signals that control mood, thoughts, pain, and other

sensations.2

Postmortem examination of brains of suicide victims suggest altered

noradrenergic activity, including increased binding to 1-, 2-, and -adrenergic

receptors in the cerebral cortex and a decreased total number and density of
http://www.holistichelp.net/holistic-treatment-for-anxiety.htmlhttp://www.holistichelp.net/sleep.htmlhttp://www.holistichelp.net/sleep.htmlhttp://www.holistichelp.net/holistic-treatment-for-anxiety.html


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noradrenergic neurons in the locus coeruleus. Involvement of the serotonin system is

suggested by findings of reduced plasma tryptophan levels, a decreased cerebrospinal

fluid level of 5-hydroxyindolacetic acid (the principal metabolite of serotonin in brain),

and decreased platelet serotonergic transporter binding. An increase in brain serotonin

receptors in suicide victims is also reported. Depletion of blood tryptophan, the amino

acid precursor of serotonin, rapidly reverses the antidepressant benefit in depressed

patients who have been successfully treated. However, a decrement in mood after

tryptophan reduction is considerably less robust in untreated patients, indicating that, if

presynaptic serotonergic dysfunction occurs in depression, it likely plays a contributing

rather than a causal role.3

Depression is treated with antidepressants that affect norepinephrine and

serotonin in the brain. The antidepressants help correct the abnormal neurotransmitter

activity. A newer drug, fluoxetine (Prozac), is a selective serotonin reuptake inhibitor

(SSRI) that appears to establish the level of serotonin required to function at a normal

level. As the name implies, the drug inhibits the re-uptake of serotonin neurotransmitter

from synaptic gaps, thus increasing neurotransmitter action. In the brain, then, the

increased serotonin activity alleviates depressive symptoms. 2

3) Generalized anxiety disorder

People with generalized anxiety disorder (GAD) experience excessive worry that causes

problems at work and in the maintenance of daily responsibilities. Evidence suggests that

GAD involves several neurotransmitter systems in the brain, including norepinephrine and

serotonin. 2
http://www.minddisorders.com/Flu-Inv/Fluoxetine.htmlhttp://www.minddisorders.com/Flu-Inv/Generalized-anxiety-disorder.htmlhttp://www.minddisorders.com/Flu-Inv/Generalized-anxiety-disorder.htmlhttp://www.minddisorders.com/Flu-Inv/Fluoxetine.html


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In experimental models of anxiety, anxiogenic agents share in common the property of

altering the binding of benzodiazepines to the -aminobutyric acid (GABA) A receptor/chloride

ion channel complex. Benzodiazepines are thought to bind two separate GABAA receptor sites:

type I, which has a broad neuroanatomic distribution, and type II, which is concentrated in the

hippocampus, striatum, and neocortex. The antianxiety effects of the various benzodiazepines

and side effects such as sedation and memory impairment are influenced by their relative binding

to type I and type II receptor sites. Serotonin [5-hydroxytriptamine (5HT)] also appears to have a

role in anxiety. Buspirone, a partial 5HT1A receptor agonist, and certain 5HT2A and 5HT2C

receptor antagonists (e.g., nefazodone) may also have beneficial effects 4.

4) Drug addictions Cocaine and crack cocaine are psychostimulants that affect neurons containing

dopamine in the areas of the brain known as the limbic and frontal cortex. When

cocaine is used, it generates a feeling of confidence and power. However, when large

amounts are taken, people "crash" and suffer from physical and emotional exhaustion

as well as depression.

Opiates, such as heroin and morphine, appear to mimic naturally occurring peptidesubstances in the brain that act as neurotransmitters with opiate activity called

endorphins. Natural endorphins of the brain act to kill pain, cause sensations of

pleasure, and cause sleepiness. Endorphins released with extensive aerobic exercise,

for example, are responsible for the "rush" that long-distance runners experience. It is

believed that morphine and heroin combine with the endorphin receptors in the brain,

resulting in reduced natural endorphin production. As a result, the drugs are needed to

replace the naturally produced endorphins and addiction occurs. Attempts to


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counteract the effects of the drugs involve using medications that mimic them, such

as nalorphine, naloxone, and naltrexone .

5) Alcohol is one of the depressant drugs in widest use, and is believed to cause its effectsby interacting with the GABA receptor. Initially anxiety is controlled, but greater

amounts reduce muscle control and delay reaction time due to impaired thinking.2
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CHAPTER V

CONCLUSION

Neurotransmitters are chemicals located and released in the brain to allow an impulse

from one nerve cell to pass to another nerve cell. Essentially they are the communication system

of the mind, body and nervous system.

Medical researchers tell us that deficiencies, imbalances, disruption or malfunctioning of

neurotransmitters is extremely common in our society and is at the root of many of common

health conditions, because when neurotransmitters are not functioning properly then the mind

and body do not communicate effectively. When communication malfunctions, then organ

systems don't function as they should. This results in a variety of undesirable symptoms both

physically and psychologically.
http://www.minddisorders.com/A-Br/Brain.htmlhttp://www.minddisorders.com/A-Br/Brain.html


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REFERENCES

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th

June 2011

2. Anonym. Neurotransmitters. Available at : http://www.minddisorders.com/Kau-Nu/Neurotransmitters.html. Accesed on 7

thJune 2011

3. Reus VI. Section 5Psychiatric Disorders 385. Mental Disorders. Avaiable at :http://www.harrisonsonline.com/. Accesed on : 7th June 2011

4. Frankenburg FR. Schizophrenia. Available at :http://emedicine.medscape.com/article/288259-overview#a0104. Accesed on 8

thJune

2011.

5. Gromisch ES. Study Guide for the Neurotransmitters in the Brain. Available at :http://www.brighthub.com/education/homework-

tips/articles/62633.aspx#ixzz1LBdObYqp . Accesed on 6th

June 2011.

6. Neurotransmitter Ande Your Health. Avaiable at :http://www.holistichelp.net/holistic-health-care.html. Accesed on 7th June 2011.

7. Synapses. Available at : http://www.biologymad.com/nervoussystem/synapses.htm. Accessed on : 12th June 2011
http://themedicalbiochemistrypage.org/nerves.htmlhttp://www.minddisorders.com/Kau-Nu/Neurotransmitters.htmlhttp://www.minddisorders.com/Kau-Nu/Neurotransmitters.htmlhttp://www.harrisonsonline.com/http://emedicine.medscape.com/article/288259-overview#a0104http://www.brighthub.com/members/kakumei.aspxhttp://www.brighthub.com/education/homework-tips/articles/62633.aspx#ixzz1LBdObYqphttp://www.brighthub.com/education/homework-tips/articles/62633.aspx#ixzz1LBdObYqphttp://www.holistichelp.net/holistic-health-care.htmlhttp://www.biologymad.com/nervoussystem/synapses.htmhttp://www.biologymad.com/nervoussystem/synapses.htmhttp://www.holistichelp.net/holistic-health-care.htmlhttp://www.brighthub.com/education/homework-tips/articles/62633.aspx#ixzz1LBdObYqphttp://www.brighthub.com/education/homework-tips/articles/62633.aspx#ixzz1LBdObYqphttp://www.brighthub.com/members/kakumei.aspxhttp://emedicine.medscape.com/article/288259-overview#a0104http://www.harrisonsonline.com/http://www.minddisorders.com/Kau-Nu/Neurotransmitters.htmlhttp://www.minddisorders.com/Kau-Nu/Neurotransmitters.htmlhttp://themedicalbiochemistrypage.org/nerves.html

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