2. CONTENTS
• Organization of NS
• Brain
• Spinal cord
• Peripheral nervous system
• Autonomic nervous system
• Neurotransmission
• Major neurotransmitters and
receptors
2
3. ORGANIZATION OF
NERVOUS SYSTEM
NERVOUS SYSTEM
PERIPHERAL NERVOUS SYSTEM CENTRAL NERVOUS SYSTEM
AUTONOMIC NERVOUS SYSTEM SOMATIC NERVOUS SYSTEM
BRAIN SPINAL CORD
PARASYMPATHETIC SYMPATHETIC
3
7. The Neuron
• Soma (cell body) – contains nucleus,
cytoplasm, organelles
• Dendrites – receive info
• Axon – transmits info
• Myelin sheath – covers the axon to
increase transmission speed (cause
of sensory and motor disturbances in
multiple sclerosis)
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8. Neuron
• Basic functional unit of nervous system
• Unique features of neuron:
– Excitability
– Conductivity
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9. What is a synapse?
• A synapse is the junction between 2
neurones.
• There is a very narrow gap of about
20nm between neurones called the
synaptic cleft.
• A nerve impulse cannot cross the
synaptic cleft, so nerve impulses are
carried by chemicals called
neurotransmitters.
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11. Action Potential/Impulse conduction
• The information in neuron is passed from one to
another in the form of nerve signal i.e. Action
potential, which is due to its unique features of
excitability and conductivity.
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12. Action Potential
• Nerve signals are transmitted by action
potential
• Any stimulus - Mechanical
Physical
Biochemical
Sudden change in resting membrane
potential
C
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14. Resting membrane potential
• Normally there is an excess of positive charges
outside the cell
• Inside of the cell is negative with respect to
outside
• Called as Resting membrane potential
Normal Resting Membrane Potential is -70mv
Due to unequal no. of ions on either side of the
membrane
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15. Resting membrane
potential
• Following are the ions which play
important role in generating resting
membrane potential :
- Sodium ions ( +vely charged)
- Potassium ions ( +vely charged)
- Chloride ions ( -vely charged)
- Organic ions ( e.g. proteins) :-vely
charged
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16. Resting membrane potential
• Na+K+Pump actively pump 3 Na+ outside
the neuron for each 2 K+ inside the neuron.
• Thus Most of the sodium ions remain
outside of the cell and Potassium ions are
inside the cell.
• This creates negative potential inside the
resting neuron -70mv
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18. Action Potential
Resting stage : - 70mv
Any stimulus – Mechanical, Physical or
Biochemical
Change in resting membrane potential
(from -70mv to +30mv)
This change in RMP causes opening of
voltage gated Na+ channel
More entry of Na+ inside the neuron
Reaches Maximum electropotential +30 to 35mv
This gradual increase in charge is called as
depolarization
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19. • Depolarization:
Each action potential begins with a sudden
change from the normal resting negative
membrane potential to a positive potential
• Repolarization :
After depolarization the action potential ends
with equally rapid change back to negative
potential
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21. The Synapse
• Axon terminal
releases
neurotransmitters.
• Neurotransmitters
cross the synapse
and bind to
receptors on
another neuron.
• Neurotransmitters
released, taken up
again by first
neuron.
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22. NEUROTRANSMITTERS
• Chemicals produced by the body that
are released from the nerve endings
• Enable passage of impulses from one
neuron to another across the synapse
• Act on their specific receptors
(glycoprotein structures on the cell
membrane)
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24. Fate of Neurotransmitter
Pre Synaptic neuron
Re
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ak
rs
e
it te
Ch
sm
a
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tra
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o
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MAO Ne
Auto Receptor
Vesicles
tors
COMT apt ic Recep
Post Syn
Post Synaptic neuron Diffusio
n of NTs
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33. Serotonin
• Serotonin - 5-Hydroxytriptamine
• Also known as 5-HT
• Known to control impulse, emotion &
behaviour
• Increased levels leads to aggression
• Reduced level may induce suicidal
thoughts
• Involved in sleep & depression
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34. Serotonin Receptors
• The serotonin receptors are called
5HT1, 5HT2, 5HT3, 5HT4, 5HT5, 5HT6 &
5HT7.
• These are further subdivided as 5HT 1A,
5HT2A,5HT1B, 5HT1D etc.
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37. AcetylCholine
• Acetylcholine is the major
neurotransmitter which controls
various activities like
1. contraction of skeletal muscles,
2. relaxation of cardiac muscles,
arousal,
3. reward,
4. memory,
5. short term learning
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39. Receptors of Acetylcholine
• The receptors of Ach are of various
types & are complicated in nature
• Muscarinic & nicotinic receptors are
important
• Muscarinic receptors M1, M2, M3 …M5
• Binding of Ach with M1 M3 M5 causes
stimulatory effects whereas binding
with M2 & M4 Causes inhibitory
action.
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43. Norepinephrine/Noradrenaline
• Noradrenaline normally produces
effects such as increased heart rate,
increased blood pressure, dilation of
pupils, dilation of air passages in the
lungs and narrowing of blood vessels
in non-essential organs. This enables
the body to perform well in stressful
situations. Increases levels of energy,
interest & Mood.
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44. Norepinephrine/Noradrenaline
• Receptors :
Alpha receptors:
- α1 receptors
Found in the blood vessels
- α2 receptors (Auto receptor)
Beta receptors:
- β 1 receptors
Mainly found in heart
- β 2 receptors
Mainly found in bronchi
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46. DOPAMINE
• Dopamine interacts with receptors on
some peripheral nerve fibers and many
central neurons (eg, in the substantia
nigra, midbrain, ventral tegmental area,
and hypothalamus).
• After release and interaction with
receptors, dopamine is actively pumped
back (reuptake) into the nerve terminal.
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47. Dopamine
• Involved in movement, attention and
learning, drive, desire motivation &
pleasure/reward
• Dopamine imbalance also involved in
schizophrenia
• Loss of dopamine- producing
neurons is cause of Parkinson’s
Disease
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48. DOPAMINE RECEPTORS
• Dopaminergic receptors are
classified as D1 through D5.
• D3 and D4 receptors play a role
in thought control (limiting the
negative symptoms of
schizophrenia); D2 receptor
activation controls the
extrapyramidal system.
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49. D2 is primarily a post synaptic receptor
whereas D3 is believed
To be a autoreceptor
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51. Gama Amino Butyric Acid
• It is primarily an inhibitory
neurotransmitter responsible for
Sleep, prevents anxiety & stress
signals & has an overall calming effect
on the brain.
• It has three receptors GABAA, GABAB
& GABAC
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54. SUBSTANCE-P
• Substance P, a peptide, occurs
in central neurons (habenula,
substantia nigra, basal ganglia,
medulla, and hypothalamus) and
is highly concentrated in the
dorsal root ganglia.
• Its release is triggered by
intense afferent painful stimuli.
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55. NITRIC OXIDE
• Nitric oxide (NO) is a labile gas that mediates
many neuronal processes.
• It is generated from arginine by NO synthase,
an enzyme that activates soluble guanylate
cyclase by binding to Ca/calmodulin
complexes.
• Thus, neurotransmitters that increase
intracellular Ca (eg, substance P, glutamate,
acetylcholine) stimulate NO synthesis in
neurons that express NO synthetase.
• NO may be an intracellular messenger; it may
diffuse out of a cell into a 2nd neuron and
produce physiologic responses (eg, long-term
potentiation [a form of learning],
neurotransmitter release and reuptake) or
enhance glutamate (NMDA) receptor-mediated
neurotoxicity.
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56. Glutamate & Aspartate
• They are excitatory neurotransmitters.
• Their receptors are of 2 types.
– Ionotropic
– N- Methyl D- Aspartate. (NMDA)
Alpha-amino-3-hydroxyl-5-methyl-4-isoxozole
propionic acid (AMPA)
– Metabotropic
Trans-1-aminoclycopentane1,3Dicarboxylicacid.
(Trans- ACPD)
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57. Drugs
• Drugs which have molecules of
similar shape to transmitter
substances can affect protein
receptors in postsynaptic
membranes.
• Drugs that stimulate a nervous
system are called AGONISTS
• Drugs that inhibit a nervous
system are called
ANTAGONISTS.
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58. NEUROTRASMISSION
• A neuron generates and propagates an
action potential along its axon, then
transmits this signal across a synapse by
releasing neurotransmitters, which
trigger a reaction in another neuron or an
effector cell (eg, muscle cells; most
exocrine and endocrine cells).
• The signal may stimulate or inhibit the
receiving cell, depending on the
neurotransmitter and receptor involved.
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59. Blood brain barrier: A mechanism that
creates a barrier between brain tissues and
circulating blood; serves to protect the central
nervous system.
Propagation: passing of electrical impulse
within neuron by exchange of Na+ and K+
across the axonal membrane.
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61. Receptors
• Specific macromolecular components of
the cell which act as a binding site with
functional correlate to produce effect
• Situated - on the surface / inside the cell
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62. Drug at Receptor
• Agonist : It activates a receptor to produce an effect
similar to that of the physiological signal molecule
• Antagonist : It prevents the action of an agonist on a
receptor but does not have any effect of its own
• Partial agonist : It activates a receptor to produce sub
maximal effect but antagonises the action of full
agonist.
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66. PHARMACODYNAMICS
• It it the quantitative study of the biological
and therapeutic effects of drugs.
• “What Drug does to the body”
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67. PHARMACOKINETICS
• It is the study of
absorption, distribution,
metabolism and excretion
of drugs
• “What Body does to the
Drug”
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68. Pharmacokinetics
• Absorption
How the drug is moved into blood stream from the site
of administration ?
• Distribution
How much drug is moved to various body tissues /
organs ? Depends on blood flow through tissue
• Metabolism
How the drug is altered – broken down ?
• Elimination
How much of the drug is removed from the body ?
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69. Absorption and Bioavailability
• Absorption is the movement of drug from its
site of administration into the circulation.
• Bioavailability : Fraction of administered dose
of a drug that reaches the systemic circulation
in the unchanged form.
– Bioavailability of IV route : 100 %
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73. DRUG EXCRETION
• Kidneys
• Lungs
• Skin
• Bile
• Milk and Saliva
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74. FACTORS MODIFYING THE
EFFECTS OF DRUG
• Body weight
• Age
• Gender.
• Diet & environment
• Route of administration
• Emotional Factors
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75. FACTORS MODIFYING
THE EFFECTS OF DRUG
• Genetic factors
• metabolic disturbances
• Presence of disease
• Other drug therapy
• Additive effect
• Antagonism - chemical
antagonism
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79. The Blood-Brain Barrier
• Endothelial cells in blood vessels in
the brain fit closely together
• Only some molecules can pass
through
• Protects the brain from foreign
molecules and hormones and
neurotransmitters from other parts of
the body
• Can be damaged by infections, head
trauma, high blood pressure, etc.
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