This document provides information about adrenaline and noradrenaline. It discusses their discovery, functions, chemistry, biosynthesis, receptors, mode of action, pathways in the brain, differences between the two, and effects of low and high levels. It also outlines some medical uses of adrenaline and noradrenaline, such as treating anaphylaxis, asthma attacks, cardiac arrest, infections, septic shock, and as medications for ADHD and depression.

3. PRESENTED BY:
SADA FATIMA
AFIFA ZAHID
MALIHA TANVEER
ANMOL SHEHZADI
MA’AM ZEEMAL SEEMAB
PRESENTED TO:

4. CONTENTS
 Introduction
 Functions
 Chemistry
 Biosynthesis
 Receptors
 Mode of action
 Pathway
 Differences
 Effect of low & high
levels
 Medical uses

5. INTRODUCTION
 Polish physiologist Napoleon Cybulski first isolated adrenaline in
1895.
 Adrenaline, also known as epinephrine, is a hormone which is
involved in regulating visceral functions. (Trigger 'alarm’ responses,
helping to prepare body for extreme efforts)
 Extreme efforts ( increase heart rate, increase blood pressure,
dilation of bronchioles, elevation in blood glucose, reduced
blood flow to skin and digestive organs and increase blood
flow to heart and muscles)
 Adrenaline is normally produced by the adrenal glands (located on
top of kidneys) and by a small number of neurons in the medulla
oblongata (hind brain).
ADRENALINE:

6.  Adrenaline prepare the body for fight-or-flight response.
 Provides muscles, heart and lungs with more oxygen.
 If adrenal medulla has removed surgically, the ability to withstand any
stress situation -such as cold- is markedly diminished.
ROLE OF ADRENALINE:

7. NORADRENALINE:
 The name "noradrenaline", derived from Latin roots meaning "at/alongside the
kidneys“
 Noradrenaline (NA) also called norepinephrine (NE), is an organic chemical in
the catecholamine family that functions in the brain and body as both
a hormone and neurotransmitter.
 The general function of norepinephrine is to mobilize the brain and body for action.
 It is secreted by certain nerve endings of the sympathetic nervous system, and by
the medulla (centre) of the adrenal glands.
 Norepinephrine release is lowest during sleep, rises during wakefulness, and
reaches much higher levels during situations of stress or danger, in the so-
called fight-or-flight response. (it is also referred to as a stress hormone.)

8. FUNCTIONS OF NORADRENALINE:
 In the brain, norepinephrine increases arousal and alertness, promotes vigilance,
enhances formation and retrieval of memory, and focuses attention; it also increases
restlessness and anxiety.
 In the eyes, an increase in production of tears, making the eyes more
moist, and pupil dilation through contraction of the iris.
 In the heart, an increase in the amount of blood pumped.
 In adipose tissue, an increase in calories burned to generate body heat (non
shivering thermogenesis)
 Constriction of blood vessels in particular area (gut) to bring an increase blood
pressure.
 In the kidneys, release of renin and retention of sodium in the bloodstream and

9. CHEMISTRY
 Other name of Noradrenaline is1-(3,4-
Dihydroxyphenyl)-2-aminoethanol.
 Molecular Formula C8H11NO3
 Average mass = 169.178 Da
 Molecular Formula of adrenaline C9H13NO3
 Molar mass =183.207 g·mol−1
 Noradrenaline structure differs from that
of adrenaline only in that adrenaline has a methyl
group attached to its nitrogen, whereas the methyl
group is replaced by a hydrogen atom in
norepinephrine

10. BIOSYNTHESIS OF NORADRENALINE
 Tyrosine → L-DOPA → Dopamine →
Norepinephrine
 Arrival of action potential → opening of calcium
channels → increase of calcium ions
(depolarization) in neuron causes the synaptic
vesicles to fuse with membrane (exocytosis) →
release of NE into the synaptic cleft.
Presynaptic
events:

11.  NE (norepinephrine) binds to post synaptic receptor on effector organ which triggers
intracellular response.
 NE also binds to presynaptic receptors which results in decrease of NE release through
negative feedback.
 Or can be metabolized to an inactive metabolites that will be excreted in the urine by
the enzyme Catechol o- methyltransferase (COMT)
 Or some NE gets transported back into the neuron by sodium chloride dependent NE
transporter (NET), So once inside the neuron NE may be either transported back into
synaptic vesicles for future use
 or it can be broken down to inactive metabolites by enzyme Monoamine oxidase
(MAO) present in neuronal mitochondria producing inactive metabolites that will
Post synaptic
events:

12. BIOSYNTHESIS OF ADRENALINE:

13.  In the adrenal medulla and in a few brain regions, noradrenaline undergoes
methylation and converted to adrenaline by the enzyme N-methyltransferase.

14. ADRENERGIC RECEPTORS:
 Adrenergic receptors are cell surface glycoproteins that recognize and
selectively bind the catecholamines, norepinephrine and epinephrine, which
are released from sympathetic nerve endings and the adrenal medulla.
 By transducing the external catecholamine stimulus into an intracellular signal,
these receptors mediate the actions of the sympathetic nervous system,
including a variety of responses.
 There are two main groups of adrenoreceptors, α and β.
• α are divided to α1 and α2.
• β are divided to β1, β2 and β3.
TYPES:

16. THE FUNCTIONS OF ALPHA ADRENERGIC RECEPTOR:
The functions of alpha adrenergic receptors is according to their
types:
Receptor Sites of action Effects
α1 smooth muscle, heart, and
liver
•Glycogenolysis
•Vasoconstriction
•Mydriasis
•Contraction and
Urinary retention
•Renin
α2 platelets, vascular smooth
muscle, nerve termini, and
pancreatic islets
platelet aggregation,
vasoconstriction, and
inhibition of NE
release and of insulin
secretion

17. THE FUNCTIONS OF BETA ADRENERGIC RECEPTOR:
The functions of beta adrenergic receptors is according to their types:
Receptor Sites of action Effects
β1 Heart
Kidney
Tachycardia,
HR, Counteractivity
and AV Conduction
Renin and BP
β2 lungs, gastrointestinal tract, liver,
uterus, vascular smooth and
skeletal muscle
Bronchodilatation
Vasodilation (Smooth
muscle relaxation),
sphincter constriction
,
β3 Fat cells Lipolysis
Relaxation of bladder

18. MODE OF ACTION
 The Major Role of adrenaline and noradrenaline is in Fight and Flight response.
 Strong emotions such as fear or anger cause epinephrine/norepinephrine to be
released into the bloodstream, that causes:
 Increase in the heart rate and the force of heart contraction so that increased
cardiac output allows more blood to be delivered around the body.
 In the blood vessels, it triggers vasoconstriction (narrowing of blood vessels),
which increases blood pressure.
 It goes to the bronchioles in your lungs and cause them to dilate so it become
easier to breath (bronchodilation).
 It causes the liver to release glucose, that can be used in the muscles as an
energy supply. (glycogenolysis)

19.  Glycogenolysis is the process of breaking down glycogen into single glucose
residues and it depends upon body's metabolic need.
 Glycogenolysis occur in starved state and in flight and fight condition.
 When our body undergoes stress condition, our body need immediate supply of
energy that comes from glucose so to increase the level of glucose, the liver cells or
skeletal muscle cells have to begin breaking down the glycogen into glucose and
release the glucose into the blood plasma.
STEPS OF GLYCOGENOLYSIS
1. Signaling of G protein coupled receptor (GPCR) by Epinephrine.
2. Activation of G proteins
3. Activation of adenylyl Cyclase and cAMP:
4. Activation of Protein Kinase A (PKA) by cAMP
5. Glycogen breakdown
GLYCOGENOLYSIS:

21. BRONCHODILATION:
 The “fight-or-flight” reaction elicited by the sympathetic system is essentially a
whole body response.
 Bronchodilation in the lungs facilitates the movement of air in and out of the lungs
so that the uptake of oxygen from the atmosphere and the elimination of carbon
dioxide from the body are maximized.
MECHANISM OF BRONCHODILATATION:
 The epinephrine produce bronchodilatation by stimulating beta 2 receptors
situated in the smooth muscle of the bronchial tree, from the trachea down to the
terminal bronchioles.
 Beta adrenergic receptors are coupled to a stimulatory G protein of adenylyl
cyclase. This enzyme produces the second messenger cyclic adenosine
monophosphate (CAMP).
 In the lung, CAMP decreases calcium concentrations within cells and activates

22.  In addition, beta₂
agonists open large
conductance calcium-
activated potassium
channels and thereby
tend to hyperpolarize
airway smooth muscle
cells.
 The combination of
decreased intracellular
calcium, increased
membrane potassium
conductance, and
decreased myosin light
chain kinase activity
leads to smooth muscle
relaxation and

23. PATHWAY IN BRAIN:

24.  Norepinephrine producing neurons in CNS primarily consisting pons and
medulla
 The most primarily neurone is the nucleus of the locus coeruleus which is the
main site of neuron production.
 Neurones in the brain that release norepinephrine are located through out
the brain stem, in the locus coeruleus. Norepinephrine producing cells are
said to be noradrenergic.
 The out put of the noradrenergic locus cerulea cells extends broadly
throughout the cerebrum including cerebrum cortex and thalamic nuclei.
 In addition the output of these cells projects prominently to the cerebellum
,pons and the spinal cord because of this why this distribution of the
projection paths noradrenergic cells in the locus coeruleus are to believed to
modulate.
 Many behavioural and physiological processes including moods, overall
arousal attention and sexual behaviour.

25.  Almost exclusively made in the adrenal
medulla.
 More Adrenaline is released from the
adrenal medulla than Noradrenaline.
 Acts mainly as a hormone and is released
primarily by the adrenal medulla into the
bloodstream. Hence, we can say that
Adrenaline is carried throughout the
whole body and acts at different organs
on different adrenergic receptors.
 Synthesised from Noradrenaline.
 Predominantly made in the sympathetic
nervous system.
 More Noradrenaline is released from the
sympathetic nervous system than
Adrenaline.
 Function mainly as a neurotransmitter at
the synapse between neurons when
released from sympathetic neurons
(stored in vesicles). Noradrenaline is
released at a small concentration as a
hormone in the blood circulation by the
adrenal medulla.
 Synthesised from Dopamine.
ADRENALINE VS NORADRENALINE

26.  Activates the alpha and beta-adrenergic
receptors, and as such, has a wide-range
effect.
 Response: dilates blood vessels in the
skeletal muscle, increases heart rate and
an increase in blood pressure,
bronchodilation, increase in
carbohydrate metabolism. The
metabolic aim is to increase energy
usage and availability.
 Activates mainly the alpha-adrenergic
receptors and acts on beta receptors to a
certain degree.
 Response: increases and maintain blood
pressure through vasoconstriction of
blood vessels and dilates coronary
arteries.

27. EFFECTS OF DEFICIENCY
Low levels of epinephrine and
norepinephrine can result in physical
and mental symptoms, such as:
• anxiety
• depression
• changes in blood pressure
• changes in heart rate
• low blood sugar, or hypoglycemia
• migraine headaches
• problems sleeping
EFFECTS OF HIGH LEVELS
Symptoms of high levels of
epinephrine or norepinephrine can
include:
• excessive sweating
• rapid or irregular heartbeat
• high blood pressure
• jitteriness or shakiness
• intense headaches
• pale or cold skin

28.  In addition to being a hormone and neurotransmitter, epinephrine is also used as a
medical treatment in its synthetic form.
 Its main use involves the treatment of anaphylaxis. This is a severe allergic reaction
that can affect a person’s breathing. An injection of epinephrine can help to open up
your airway so you can breathe.
 Other uses of epinephrine include:
• Asthma attacks. An inhaled form of epinephrine can help treat or prevent severe
asthma attacks.
• Cardiac arrest. An epinephrine injection may restart your heart if your heart has
stopped pumping (cardiac arrest).
• Infection. If you have a severe infection and aren’t producing enough
catecholamines, you may need to be given epinephrine through an intravenous line
(IV).
MEDICAL USES OF ADRENALINE:

29. MEDICAL USES OF NORADRENALINE:
 Doctors sometimes use norepinephrine to treat septic shock, a severe infection
that can lead to organ failure. This infection tends to cause dangerously low
blood pressure. Norepinephrine given through an IV can help to constrict
blood vessels, increasing blood pressure.
 Some people with ADHD or depression take medications that stimulate or
increase the release of norepinephrine, including:
• atomoxetine (Strattera)
• serotonin-norepinephrine reuptake inhibitors, such as duloxetine (Cymbalta)
and venlafaxine (Effexor XR)