NEUROTRANSMISSION introduction , steps involved

NEUROTRANSMISSION
GENERAL ASPECTS AND STEPS INVOLVED IN
NEUROTRANSMISSION
Department of Pharmacology
Subject incharge :
Dr. Vijaya Kumar S M Pharm., PhD.,
Associate Professor
Presentation by :
SIDDARAMAIAH.K S
1st sem M Pharm

INTRODUCTION :
DEFINITION:
Neurotransmitters are chemical messengers that transmit signals from a
neuron to a target cell across a synapse.
 Target cell may be a neuron or some other kind of cell like a muscle or
gland cell.
 Neurotransmitters are packaged into synaptic vesicles presynaptic side of a
synapse.
Department of Pharmacology SREE SIDDAGANGA COLLEGE OF PHARMACY

A SCHEMATIC REPRESENTATION OF A
CHEMICAL SYNAPSE

PROPERTIES OF
NEUROTRANSMITTERS:
1.Synthesized in the presynaptic neuron.
2.Localized to vesicles in the presynaptic neuron.
3.Released from the presynaptic neuron under
physiological condition.
4.Rapidly removed from the synaptic cleft by uptake or
degradation
5.Presence of receptor on the post-synaptic neuron.
6.Binding to the receptor causes a biological response.

There are more than 40 neurotransmitters in the human nervous system; some of the
most important are acetylcholine, norepinephrine, dopamine, gamma- aminobutyric
acid (GABA), glutamate, serotonin, and histamine.
Key facts about neurotransmitters
Excitatory neurotransmitters Glutamate (Glu)
Acetylcholine (ACh)
Histamine
Dopamine (DA)
Norepinephrine (NE); also known as noradrenaline (NAd)
Epinephrine (Epi); also known as adrenaline (Ad)
Inhibitory neurotransmitters gamma-Aminobutyric acid (GABA)
Serotonin (5-HT)
Dopamine (DA)
Neuromodulators Dopamine (DA)
Serotonin (5-HT)
Acetylcholine (ACh)
Histamine
Norepinephrine (NE)
Neurohormones Releasing hormones from hypothalamus
Oxytocin (Oxt)
Vasopressin; also known as antidiuretic hormone (ADH)

DALE’S PRINCIPLE:
 OLD VIEW: Each neuron releases one, and only one
neurotransmitter.
 NEW VIEW: Neurons typically contain two +
neurotransmitters(classical and non-classical)

ACETYLCHOLINE(Ach):
• Acetylcholine was the first neurotransmitter to be discovered.
• Isolated in 1921 by a German biologist named Otto Loewi.
• Uses choline as a precursor - cholinergic neurotransmitter.
Autonomic Nervous system – Acetylcholine act as a
neurotransmitter in both the sympathetic and parasympathetic
branches of autonomic nervous system regulating involuntary
function such as heart rate, digestion etc..

Neuromuscular junction – acetylcholine transmitting signals from
motor neurons to muscle fibers at neuromuscular junction , leading to
muscle contraction.
Synaptic transmission – acetylcholine involved in synaptic
transmission in central and peripheral nervous systems

DOPAMINE:
• Dopamine is primarily synthesized in certain neurons within the brain
particularly in two main region :
Substantia nigra – This region located in the midbrain contains
dopaminergic neurons that synthesize dopamine,
Parkinson’s disease , neurodegenerative disorder characterized by a
loss of dopamine-producing neurons in this area.

Vent mesencephalon and hypothalamus – these region also contain
dopaminergic neurons involved in regulating various functions such as
mood, motivation and attention.
Schizophrenics have too much dopamine.
• Dopamine – Released from the neuron into the synaptic cleft, where it
can bind to dopamine receptors on target neurons and exert its effects.
Any excess dopamine not used for signaling is reabsorbed by the
presynaptic neuron through a process called reuptake or broken down
by enzymes like monoamine oxidase (MAO) to be recycled or
excreted.

NOREPINEPRINE(nor adrenaline):
• Synthesized in the adrenal medulla and in neurons of
the central nervous system.
• Synthesized primarily in the locus coeruleus, which is
a nucleus in brainstem. Its released from nerve
terminals and acts on various receptors throughout the
body.
• Direct precursor to epinephrine.
• It is synthesized in four steps from tyrosine.
• Synthesized within vesicles
• Norepinephrine is strongly associated with bringing
our nervous systems into “high alert”

GLUTAMATE:
• It is an amino acid
• It is the most commonly found excitatory
neurotransmitter in the brain.
• It is involved in most aspects of normal brain function
including cognition, memory and learning.
• Glutamate is formed from alpha- ketoglutarate, an
intermediate of Kreb’s cycle.
• Glutamate involved in several neurological disorders
including Alzheimer’s disease ,Parkinson’s disease and
epilepsy.

GAMA –AMINO BUTYRIC
ACID(GABA):
• Synthesized directly from glutamate through the action of enzyme
glutamate decarboxylase(GAD) , This process involved the conversion of
glutamate to GABA in the presence of vitamin B6 (pyridoxal phosphate)
which act as cofactor for GAD .
• GABA synthesis occurs primarily within GABAergic neurons, where it is
then packaged into synaptic cleft upon neuronal stimulation.
• GABA is the inhibitory neurotransmitter.
• Present in high concentrations in the CNS, preventing the brain from
becoming overexcited.
• If GABA is lacking in certain parts of the brain, epilepsy results.

SEROTONIN(5-HT):
• Serotonin also know as 5-hydroxytryptamine (5HT) is a
neurotransmitter primarily involved in regulating mood,
appetite, sleep and cognition . Its action in brain is complex and
involves various receptor subtypes such as 5-HT1, 5-HT2,
5-HT3 etc…
• Synthesized in two steps from the amino acid tryptophan.
• Regulates attention and other complex cognitive functions,
such as sleep(dreaming), eating, mood, pain regulation.
• Too little serotonin has been shown to lead to depression, anger
etc.

NEUROTRANSMITTERS:
Neurotransmitter Function Effect of Deficit Effect of surplus
ACETYLCHOLINE EXCITATORY;
Released by motor
neurons, stimulates
muscle contraction;
involved in attention,
memory, learning and
general intellectual
functioning.
ALZHEMIER’S
DISEASE
Severe muscle spasms
DOPAMINE INHIBITORY:
Pleasurable sensations
involved in voluntary
movement, attention and
learning.
Parkinson’s disease Schizophrenia
Drug Addiction

SEROTONIN FUNCTION EFFECT OF DEFICIT EFFECT OF SURPLUS
Serotonin Inhibitory:
Moods and emotional
stress, hunger
regulation of sleep
and wakefulness
Depression mood
disorders
Autism
Norepinephrine Excitatory:
Used for arousal in
the flight/fight
response, modulation
of mood, plays a role
in learning and
memory retrieval
Mental disorders,
especially depression.
Anxiety
GABA Inhibitory:
Helps to offset
excitatory messages
and regulate daily
sleep-wake cycles
Anxiety, seizures,
tremors and insomnia
Sleep and eating
disorders

STEPS IN NEUROTRANSMITTER PROCESSING ARE:
• SYNTHESIS: Neurotransmitters are synthesized by the
enzymatic transformation of precursors.
• STORAGE: They are packaged inside synaptic vesicles.
• RELEASE: They are released from presynaptic terminal by
exocytosis when calcium enters axon terminal during an
action potential. Diffuse across the synaptic cleft to the
postsynaptic membrane.

• BINDING: They bind to receptor proteins.
• INACTIVATION: The neurotransmitter is degraded either by being
broken down enzymatically, or reused by active reuptake

REFERENCE:
• Pharmacology textbook by H.P. RANG, M.M. DALE, J.M. RITTER, P.K.
MOORE.
• Basic and clinical pharmacology by B.G. KATZUNG.
• Pharmacology textbook by Tripati.

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