BIOGENIC AMINES

DEPARTEMEN BIOKIMIA
FAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH SUMATERA UTARA
2019
•Potensial Aksi ?
TYPES OF NEUROTRANSMITTERS
• There are two kinds of neurotransmitters
– INHIBITORY and EXCITATORY.
• Excitatory neurotransmitters are not necessarily exciting – they are what
stimulate the brain.
• Those that calm the brain and help create balance are called inhibitory.
Inhibitory neurotransmitters balance mood and are easily depleted when the
excitatory neurotransmitters are overactive.
NEUROTRANSMITTER MOLECULES
• Neurotransmitters can be broadly split into two groups – the ‘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)
• This acquired knowledge about the neurotransmitters has led to the development
of successful products for many brain disorders including epilepsy,
schizophrenia, Parkinson’s disease, depression, anxiety disorders and migraine .
SEROTONIN

• SEROTONIN is an inhibitory neurotransmitter – which means that it does not

stimulate the brain.
• Adequate amounts of serotonin are necessary for a stable mood and to balance any
excessive excitatory (stimulating) neurotransmitter firing in the brain.
• If you use stimulant medications or caffeine in your daily regimen – it can cause a
depletion of serotonin over time.
• Low serotonin levels leads to an increased appetite for carbohydrates (starchy foods)
and trouble sleeping, which are also associated with depression and other emotional
disorders. It has also been tied to migraines, irritable bowel syndrome, and
fibromyalgia.
• Low serotonin levels are also associated with decreased immune system
function.
• In addition to mood control, serotonin has been linked with a wide variety of
functions, including the regulation of sleep, pain perception, body
temperature, blood pressure and hormonal activity
• These serotonergic pathways spread extensively throughout the brainstem ,
the cerebral cortex and the spinal cord .
• Largest amount of serotonin is found in the intestinal mucosa.
• Although the CNS contains less than 2% of the total serotonin in the body,
serotonin plays a very important role in a range of brain functions. It is
synthesized from the amino acid tryptophan.
HISTAMINE
• Histidine is the precursor of an important neurotransmitter histamine.
• Histamine is present in venom and other stinging secretions.
• Within the brain, histamine is produced both by mast cells and by certain neuronal fibers.
• They are prevalent in the thalamus, hypothalamus, duramater, leptomeninges, and
choroid plexus. Histaminergic neuronal cell bodies in the human are found in the
tuberomamillary nucleus of the posterior basal hypothalamus. The fibers project into
nearly all areas of the CNS, including the cerebral cortex, the brainstem, and spinal cord.
• Histamine is a biogenic amine involved in local immune responses
• Regulate physiological function in the gut
• Triggers the inflammatory response.
• Storage and release- Mast cells or basophils.
• Most histamine in the body is stored in granules in mast cells or in white blood
cells called basophils. Mast cells are especially numerous at sites of potential
injury - the nose, mouth, and feet, internal body surfaces, and blood vessels.
• Non-mast cell histamine is found in several tissues, including the brain, where it
functions as a neurotransmitter.
• Another important site of histamine storage and release is the enterochromaffin-
like (ECL) cell of the stomach.
• newly synthesized neuronal histamine is stored within the nerve terminal
vesicle. Depolarization of nerve terminals activates the exocytotic release of
histamine by voltage-dependent as well as a calcium-dependent mechanism.
MECHANISM OF ACTION

• Histamine exerts its actions by combining with specific cellular histamine

receptors. The four histamine receptors that have been discovered are
designated H1 through H4.
TYPE, LOCATION, FUNCTION OF RECEPTORS
• H1 receptors: Found on smooth muscle, endothelium, and central nervous system tissue.
Causes vasodilatation, bronchoconstriction, and pain and itching due to insect stings.
These are the primary receptors involved in allergic rhinitis symptoms, motion sickness
and sleep regulation.
• H2 receptors: Located on parietal cells of stomach, brain and cardiac muscle.
Primarily stimulate gastric acid secretion.
• H3 receptor: Found on central nervous system and to a lesser extent on peripheral
nervous system tissue.
• H4 receptor: Found primarily in the basophils and in the bone marrow. It is also found
on thymus, small intestine, spleen and colon  Plays a role in chemotaxis.
CATECHOLAMINES

• Neurotransmitters of this group share 2 chemical similarities: one core

structure of catechol and an amine group
• This group of neurotransmitters includes dopamine (DA), norepinephrine
(NE)/noradrenaline, and epinephrine (EPI)/adrenaline, and they are found
within the CNS, PNS, and adrenal glands.
DOPAMINE

• Only in central nervous system

mostly inhibitory systems
all metabotropic
• Schizophrenia
• Movement
Nigrostriatal Pathway
• At least 5 DA-R types: D1, D2, etc. ~
• DOPAMINE is our main focus neurotransmitter.  When dopamine is either
elevated or low – we can have focus issues such as not remembering where
we put our keys, forgetting what a paragraph said when we just finished
reading it or simply daydreaming and not being able to stay on task. 
• Dopamine is also responsible for our drive or desire to get things done – or
motivation. 
• Common symptoms with low dopamine levels are loss of motor control,
addictions, cravings, compulsions, and loss of satisfaction.
• When dopamine levels are elevated symptoms may manifest in the form of
anxiety or hyperactivity.
• Drugs like cocaine, opium, heroin, and alcohol increase the levels of dopamine, as
does nicotine.
• The severe mental illness schizophrenia has been shown to involve excessive
amounts of dopamine in the frontal lobes, and drugs that block dopamine are used
to help schizophrenics. 
• On the other hand, too little dopamine in the motor areas of the brain are
responsible for Parkinson's disease, which involves uncontrollable muscle tremors. 
• Dopamine is a derivative of the amino acid tyrosine. Dopamine is produced by
neurons located in a part of the brain called the Substantia Nigra (Black
Substance), which is part of the Basal Ganglia (a group of structures in the
midbrain).
• Dopamine is also a neurohormone released by the hypothalamus. Its main
function as a hormone is to inhibit the release of Prolactin from the anterior
lobe of the Pituitary.
• Dopamine can have either an excitatory or inhibitory effect on the
postsynaptic potential. When dopamine leaves the presynaptic neuron and
goes into the synapse, it can then bind to receptors on the postsynaptic
neuron.
• After dopamine is bound to the postsynaptic cell, it can either facilitate an
action potential or inhibit it. A neuron that classically releases dopamine is
called a dopaminergic neuron.
FUNCTIONS
• Dopamine plays a significant role in the cardiovascular, renal, hormonal, and
central nervous systems.
• Dopamine is useful in the management of states of low cardiac output, associated
with compromised renal function as with cardiogenic and hypovolemic shock.
• Dopamine also causes the release of norepinephrine from nerve terminals, which
contributes to its effects on the heart.
•  Dopamine usually increases the systolic and pulse pressure and either has no
effect on the diastolic blood pressure or increases it slightly.
• Dopamine produces positive chronotropic and inotropic effects on the
myocardium, resulting in increased heart rate and cardiac contractility.
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Major Dopaminergic (DA) pathways

• Nigrostriatal (substantia nigra to striatum)

• Mesolimbic/mesocortical (ventral tegmental midbrain to

n.accumbens, hippocampus, and cortex)

• Tuberoinfundibular (arcuate nucleus of hypothalamus to

median eminence then anterior pituitary)

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DOPAMINE SYNTHESIS NOREPINEPHRINE &
EPINEPHRINE
• Peripheral N.S.
Sympathetic neuroeffector junction
Adrenal glands
• Central N.S.
Hypothalamus
Locus coeruleus
• α & β groups of receptor subtypes
metabotropic ~
• NOREPINEPHRINE is an excitatory neurotransmitter that is responsible for
stimulatory processes in the body.  Norepinephrine helps to make
epinephrine as well.  This neurotransmitter can cause ANXIETY at elevated
excretion levels as well as some “MOOD DAMPENING” effects. 

Low levels of norepinephrine are associated with:

• Low Energy,
• Decreased Focus ability and
• Sleep cycle problems.
EPINEPHRINE
• EPINEPHRINE is an excitatory neurotransmitter that is reflective of stress. 
• This neurotransmitter will often be elevated when ADHD like symptoms are
present. 
• Long term STRESS or INSOMNIA can cause epinephrine levels to be depleted. 
• Epinephrine also regulates HEART RATE and BLOOD PRESSURE.
• Low levels of epinephrine contribute to fatigue, weight gain and poor
concentration.
• Elevated levels of epinephrine can be factors contributing to restlessness,
anxiety, sleep problems, or acute stress.
• FUNCTIONS
• Regulators of carbohydrate and lipid metabolism.
• Increase the degradation of glycogen and TG.
• Increase blood pressure and output of heart.
CATECHOLAMINES DEGRADATION
• There are two enzymes mainly involved in the breakdown of catecholamines,
catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).
• dopamine has only one major metabolite  homovanillic acid (HVA).
• Norepinephrine has two major metabolites  3-methoxy-4-hydroxy-phenylglycol
(MHPG) and vanillymandelic acid (VMA).
• Measurement of these metabolites in various fluid compartments (i.e., blood, urine,
and cerebrospinal fluid) facilitate in determining the possible involvement of these
neurotransmitters in mental disorders such as schizophrenia and depression.
• MAO inhibitors: the treatment of depression.
• COMT inhibitors: as a supplemental therapy to enhance the effectiveness of L-
DOPA in treating Parkinson’s disease.
 IMPORTANT MONOAMINE
METABOLITES FORMED IN THE CNS

• NE MAO, COMT MHPG (MOPEG)

• DA  MAO, COMT HVA

• 5HT  MAO  5HIAA